Re: [gmx-users] Interaction study for peptide-receptor..
Hi, Your expectation from MD is too much than reality. Peptide design is an open problem. Lots of elegant protocols are available. However, to my understanding, the core problem is still about protein-peptide docking and scoring. MD simulation only helps on some special cases. It is impossible that MD simulation is used to for screening peptide library. Best Shiyong On Thu, Oct 4, 2012 at 9:16 PM, rama david ramadavidgr...@gmail.com wrote: Thank you for reply, I read the recently published article in Biochemistry. They worked on the same receptor that I am working. ( as I mention in my previous mail) They used NAMD software and I am using gromacs. They sliced the receptor binding site and used the the solid support to the binding site and did simulation. So if I freeze the group is it will ok ?? Is it possible in gromacs to fix the residue on solid immobilized surface. If it is how to do it?? my question is How to decide which group are remove and which group should keep in simulation. thank you in advance Thank you for giving your valuable time and advice to me. With best wishes and regards, Rama david On Thu, Oct 4, 2012 at 6:11 PM, Thomas Evangelidis teva...@gmail.comwrote: I don't think AutoDock and Vina are suitable for peptide docking. I would first try the FlexPepDocking module of Rosetta which does ab initio folding of the peptide on the receptor, while moving the side-chains of the protein but leaves its backbone intact. Rosetta implements a knowledge-based scoring, which has been specifically designed for this task and is as fast as Vina or AutoDock. I would first do that and if I wouldn't get any reasonable results then I would move to MD starting from the top scored protein-peptide complexes created by Rosetta. Thomas On 4 October 2012 15:08, rama david ramadavidgr...@gmail.com wrote: Hi francesco, Thank you For reply. I did docking but the result are not so impressive. I used vina and autodock. I also did virtual screening in autodock but the result are not upto the mark. Is the freezing of group can affect my system?? How much efficiency I get by these work?? As these group are going to freeze in four simulation so if it affect one ligand it affect other ligand also. I read article that did the work like me , they sliced the binding residues and used the inert solid sphere to support binding residues instead of the freezing group other group. I think both way should have same effect..Am I right or wrong?? If you have any other way please suggest it.. With best wishes and regards Rama david On Thu, Oct 4, 2012 at 5:07 PM, francesco oteri francesco.ot...@gmail.comwrote: Hi, as far as I know, freezing just set velocities to 0 so you gain nothing freezing atoms. By the way, have you tried docking? It takes into account multiple conformation and orientation of the peptide and, depending upon the implemented algorithm, also protein sidechain orientation. Francesco 2012/10/4 rama david ramadavidgr...@gmail.com thank you Justin for reply. I dont know about long range interactions. But as I freeze the group I think it will improve my computational speed. So is there any way to find out or decide which group should be freeze, and which group should affect my interaction most probably?? Should I do Essential Dynamics ??? or Principle component analysis ??? Would you suggest me any general protocol for such work?? Thank you in Advance With Best Wishes and regards. Rama David On Thu, Oct 4, 2012 at 3:57 PM, Justin Lemkul jalem...@vt.edu wrote: On 10/4/12 2:01 AM, rama david wrote: Hi gromacs Friends, I want to do peptide-receptor ( Protein) interaction study.Receptor consist a single chain. Peptide is made up of 4 amino acids. I know the interaction pattern of peptide and receptor. I plan to mutate single residue each at a time and run 4 simulation . So I will have the 4 different simulation that contain the mutated residues and the wild one. Then afterward from the interaction energy I want to select the peptide which is showing stronger interaction than others. As mention I know the binding site, If I freeze the remaining portion in receptor that not involved in binding , Is it going to affect my screening process ??? Potentially. Do you know that the binding interactions and the mutations will only perturb local residues? Do you know that there are no long-range motions to be considered? I think you gain very little by freezing portions of the system, and risk more than you gain. -Justin --
Re: [gmx-users] Interaction study for peptide-receptor..
On 10/9/12 8:43 PM, Liu Shiyong wrote: Hi, Your expectation from MD is too much than reality. Peptide design is an open problem. Lots of elegant protocols are available. However, to my understanding, the core problem is still about protein-peptide docking and scoring. MD simulation only helps on some special cases. It is impossible that MD simulation is used to for screening peptide library. I would hardly call 4 different mutants a library. Plenty of methods exist to enhance the sampling of such systems and have been used to great effect. Computationally expensive to pull off properly? Yes. Impossible? In this case, I would say no. -Justin On Thu, Oct 4, 2012 at 9:16 PM, rama david ramadavidgr...@gmail.com wrote: Thank you for reply, I read the recently published article in Biochemistry. They worked on the same receptor that I am working. ( as I mention in my previous mail) They used NAMD software and I am using gromacs. They sliced the receptor binding site and used the the solid support to the binding site and did simulation. So if I freeze the group is it will ok ?? Is it possible in gromacs to fix the residue on solid immobilized surface. If it is how to do it?? my question is How to decide which group are remove and which group should keep in simulation. thank you in advance Thank you for giving your valuable time and advice to me. With best wishes and regards, Rama david On Thu, Oct 4, 2012 at 6:11 PM, Thomas Evangelidis teva...@gmail.comwrote: I don't think AutoDock and Vina are suitable for peptide docking. I would first try the FlexPepDocking module of Rosetta which does ab initio folding of the peptide on the receptor, while moving the side-chains of the protein but leaves its backbone intact. Rosetta implements a knowledge-based scoring, which has been specifically designed for this task and is as fast as Vina or AutoDock. I would first do that and if I wouldn't get any reasonable results then I would move to MD starting from the top scored protein-peptide complexes created by Rosetta. Thomas On 4 October 2012 15:08, rama david ramadavidgr...@gmail.com wrote: Hi francesco, Thank you For reply. I did docking but the result are not so impressive. I used vina and autodock. I also did virtual screening in autodock but the result are not upto the mark. Is the freezing of group can affect my system?? How much efficiency I get by these work?? As these group are going to freeze in four simulation so if it affect one ligand it affect other ligand also. I read article that did the work like me , they sliced the binding residues and used the inert solid sphere to support binding residues instead of the freezing group other group. I think both way should have same effect..Am I right or wrong?? If you have any other way please suggest it.. With best wishes and regards Rama david On Thu, Oct 4, 2012 at 5:07 PM, francesco oteri francesco.ot...@gmail.comwrote: Hi, as far as I know, freezing just set velocities to 0 so you gain nothing freezing atoms. By the way, have you tried docking? It takes into account multiple conformation and orientation of the peptide and, depending upon the implemented algorithm, also protein sidechain orientation. Francesco 2012/10/4 rama david ramadavidgr...@gmail.com thank you Justin for reply. I dont know about long range interactions. But as I freeze the group I think it will improve my computational speed. So is there any way to find out or decide which group should be freeze, and which group should affect my interaction most probably?? Should I do Essential Dynamics ??? or Principle component analysis ??? Would you suggest me any general protocol for such work?? Thank you in Advance With Best Wishes and regards. Rama David On Thu, Oct 4, 2012 at 3:57 PM, Justin Lemkul jalem...@vt.edu wrote: On 10/4/12 2:01 AM, rama david wrote: Hi gromacs Friends, I want to do peptide-receptor ( Protein) interaction study.Receptor consist a single chain. Peptide is made up of 4 amino acids. I know the interaction pattern of peptide and receptor. I plan to mutate single residue each at a time and run 4 simulation . So I will have the 4 different simulation that contain the mutated residues and the wild one. Then afterward from the interaction energy I want to select the peptide which is showing stronger interaction than others. As mention I know the binding site, If I freeze the remaining portion in receptor that not involved in binding , Is it going to affect my screening process ??? Potentially. Do you know that the binding interactions and the mutations will only perturb local residues? Do you know that there are no long-range motions to be considered? I think you gain very little by freezing portions of the system, and risk more than you gain. -Justin -- ==**== Justin A. Lemkul, Ph.D. Research Scientist
Re: [gmx-users] Interaction study for peptide-receptor..
Justin, Single mutation for four residue. The number of mutants is 4x19=76 Of course , that is a tiny peptide library. Best Shiyong On Wed, Oct 10, 2012 at 9:06 AM, Justin Lemkul jalem...@vt.edu wrote: On 10/9/12 8:43 PM, Liu Shiyong wrote: Hi, Your expectation from MD is too much than reality. Peptide design is an open problem. Lots of elegant protocols are available. However, to my understanding, the core problem is still about protein-peptide docking and scoring. MD simulation only helps on some special cases. It is impossible that MD simulation is used to for screening peptide library. I would hardly call 4 different mutants a library. Plenty of methods exist to enhance the sampling of such systems and have been used to great effect. Computationally expensive to pull off properly? Yes. Impossible? In this case, I would say no. -Justin On Thu, Oct 4, 2012 at 9:16 PM, rama david ramadavidgr...@gmail.com wrote: Thank you for reply, I read the recently published article in Biochemistry. They worked on the same receptor that I am working. ( as I mention in my previous mail) They used NAMD software and I am using gromacs. They sliced the receptor binding site and used the the solid support to the binding site and did simulation. So if I freeze the group is it will ok ?? Is it possible in gromacs to fix the residue on solid immobilized surface. If it is how to do it?? my question is How to decide which group are remove and which group should keep in simulation. thank you in advance Thank you for giving your valuable time and advice to me. With best wishes and regards, Rama david On Thu, Oct 4, 2012 at 6:11 PM, Thomas Evangelidis teva...@gmail.comwrote: I don't think AutoDock and Vina are suitable for peptide docking. I would first try the FlexPepDocking module of Rosetta which does ab initio folding of the peptide on the receptor, while moving the side-chains of the protein but leaves its backbone intact. Rosetta implements a knowledge-based scoring, which has been specifically designed for this task and is as fast as Vina or AutoDock. I would first do that and if I wouldn't get any reasonable results then I would move to MD starting from the top scored protein-peptide complexes created by Rosetta. Thomas On 4 October 2012 15:08, rama david ramadavidgr...@gmail.com wrote: Hi francesco, Thank you For reply. I did docking but the result are not so impressive. I used vina and autodock. I also did virtual screening in autodock but the result are not upto the mark. Is the freezing of group can affect my system?? How much efficiency I get by these work?? As these group are going to freeze in four simulation so if it affect one ligand it affect other ligand also. I read article that did the work like me , they sliced the binding residues and used the inert solid sphere to support binding residues instead of the freezing group other group. I think both way should have same effect..Am I right or wrong?? If you have any other way please suggest it.. With best wishes and regards Rama david On Thu, Oct 4, 2012 at 5:07 PM, francesco oteri francesco.ot...@gmail.comwrote: Hi, as far as I know, freezing just set velocities to 0 so you gain nothing freezing atoms. By the way, have you tried docking? It takes into account multiple conformation and orientation of the peptide and, depending upon the implemented algorithm, also protein sidechain orientation. Francesco 2012/10/4 rama david ramadavidgr...@gmail.com thank you Justin for reply. I dont know about long range interactions. But as I freeze the group I think it will improve my computational speed. So is there any way to find out or decide which group should be freeze, and which group should affect my interaction most probably?? Should I do Essential Dynamics ??? or Principle component analysis ??? Would you suggest me any general protocol for such work?? Thank you in Advance With Best Wishes and regards. Rama David On Thu, Oct 4, 2012 at 3:57 PM, Justin Lemkul jalem...@vt.edu wrote: On 10/4/12 2:01 AM, rama david wrote: Hi gromacs Friends, I want to do peptide-receptor ( Protein) interaction study.Receptor consist a single chain. Peptide is made up of 4 amino acids. I know the interaction pattern of peptide and receptor. I plan to mutate single residue each at a time and run 4 simulation . So I will have the 4 different simulation that contain the mutated residues and the wild one. Then afterward from the interaction energy I want to select the peptide which is showing stronger interaction than others. As mention I know the binding site, If I freeze the remaining portion in receptor that not involved in binding , Is it going to affect my screening process ??? Potentially. Do you know that the binding interactions and
Re: [gmx-users] Interaction study for peptide-receptor..
On 10/9/12 9:17 PM, Liu Shiyong wrote: Justin, Single mutation for four residue. The number of mutants is 4x19=76 Of course , that is a tiny peptide library. Of course one can design many different mutants with a 4-residue peptide (far more than 76 in fact, considering all possible combinations of all 20 amino acids), but I do not believe that is the intent of the OP here. Referring to the original post: http://lists.gromacs.org/pipermail/gmx-users/2012-October/075182.html It seems that 4 total simulations are intended (perhaps 4 simulations with replicates). -Justin On Wed, Oct 10, 2012 at 9:06 AM, Justin Lemkul jalem...@vt.edu wrote: On 10/9/12 8:43 PM, Liu Shiyong wrote: Hi, Your expectation from MD is too much than reality. Peptide design is an open problem. Lots of elegant protocols are available. However, to my understanding, the core problem is still about protein-peptide docking and scoring. MD simulation only helps on some special cases. It is impossible that MD simulation is used to for screening peptide library. I would hardly call 4 different mutants a library. Plenty of methods exist to enhance the sampling of such systems and have been used to great effect. Computationally expensive to pull off properly? Yes. Impossible? In this case, I would say no. -Justin On Thu, Oct 4, 2012 at 9:16 PM, rama david ramadavidgr...@gmail.com wrote: Thank you for reply, I read the recently published article in Biochemistry. They worked on the same receptor that I am working. ( as I mention in my previous mail) They used NAMD software and I am using gromacs. They sliced the receptor binding site and used the the solid support to the binding site and did simulation. So if I freeze the group is it will ok ?? Is it possible in gromacs to fix the residue on solid immobilized surface. If it is how to do it?? my question is How to decide which group are remove and which group should keep in simulation. thank you in advance Thank you for giving your valuable time and advice to me. With best wishes and regards, Rama david On Thu, Oct 4, 2012 at 6:11 PM, Thomas Evangelidis teva...@gmail.comwrote: I don't think AutoDock and Vina are suitable for peptide docking. I would first try the FlexPepDocking module of Rosetta which does ab initio folding of the peptide on the receptor, while moving the side-chains of the protein but leaves its backbone intact. Rosetta implements a knowledge-based scoring, which has been specifically designed for this task and is as fast as Vina or AutoDock. I would first do that and if I wouldn't get any reasonable results then I would move to MD starting from the top scored protein-peptide complexes created by Rosetta. Thomas On 4 October 2012 15:08, rama david ramadavidgr...@gmail.com wrote: Hi francesco, Thank you For reply. I did docking but the result are not so impressive. I used vina and autodock. I also did virtual screening in autodock but the result are not upto the mark. Is the freezing of group can affect my system?? How much efficiency I get by these work?? As these group are going to freeze in four simulation so if it affect one ligand it affect other ligand also. I read article that did the work like me , they sliced the binding residues and used the inert solid sphere to support binding residues instead of the freezing group other group. I think both way should have same effect..Am I right or wrong?? If you have any other way please suggest it.. With best wishes and regards Rama david On Thu, Oct 4, 2012 at 5:07 PM, francesco oteri francesco.ot...@gmail.comwrote: Hi, as far as I know, freezing just set velocities to 0 so you gain nothing freezing atoms. By the way, have you tried docking? It takes into account multiple conformation and orientation of the peptide and, depending upon the implemented algorithm, also protein sidechain orientation. Francesco 2012/10/4 rama david ramadavidgr...@gmail.com thank you Justin for reply. I dont know about long range interactions. But as I freeze the group I think it will improve my computational speed. So is there any way to find out or decide which group should be freeze, and which group should affect my interaction most probably?? Should I do Essential Dynamics ??? or Principle component analysis ??? Would you suggest me any general protocol for such work?? Thank you in Advance With Best Wishes and regards. Rama David On Thu, Oct 4, 2012 at 3:57 PM, Justin Lemkul jalem...@vt.edu wrote: On 10/4/12 2:01 AM, rama david wrote: Hi gromacs Friends, I want to do peptide-receptor ( Protein) interaction study.Receptor consist a single chain. Peptide is made up of 4 amino acids. I know the interaction pattern of peptide and receptor. I plan to mutate single residue each at a time and run 4 simulation . So I will have the 4 different simulation that contain the mutated residues and the wild
Re: [gmx-users] Interaction study for peptide-receptor..
Hi, Yes it is possible to screen peptides as ligand. But for these following information is needed 1. Binding site of peptide and ligand 2. Which residues in peptide are important for binding. After you simply do the mutation on the desired peptide.Performed the MD upto 50 ns Find the interaction energy. As the MD need a lot of time , you can´t use it for the large library. I plan to do only 5 simulation. With best wishes and regards. Rama david On Wed, Oct 10, 2012 at 6:54 AM, Justin Lemkul jalem...@vt.edu wrote: On 10/9/12 9:17 PM, Liu Shiyong wrote: Justin, Single mutation for four residue. The number of mutants is 4x19=76 Of course , that is a tiny peptide library. Of course one can design many different mutants with a 4-residue peptide (far more than 76 in fact, considering all possible combinations of all 20 amino acids), but I do not believe that is the intent of the OP here. Referring to the original post: http://lists.gromacs.org/**pipermail/gmx-users/2012-**October/075182.htmlhttp://lists.gromacs.org/pipermail/gmx-users/2012-October/075182.html It seems that 4 total simulations are intended (perhaps 4 simulations with replicates). -Justin On Wed, Oct 10, 2012 at 9:06 AM, Justin Lemkul jalem...@vt.edu wrote: On 10/9/12 8:43 PM, Liu Shiyong wrote: Hi, Your expectation from MD is too much than reality. Peptide design is an open problem. Lots of elegant protocols are available. However, to my understanding, the core problem is still about protein-peptide docking and scoring. MD simulation only helps on some special cases. It is impossible that MD simulation is used to for screening peptide library. I would hardly call 4 different mutants a library. Plenty of methods exist to enhance the sampling of such systems and have been used to great effect. Computationally expensive to pull off properly? Yes. Impossible? In this case, I would say no. -Justin On Thu, Oct 4, 2012 at 9:16 PM, rama david ramadavidgr...@gmail.com wrote: Thank you for reply, I read the recently published article in Biochemistry. They worked on the same receptor that I am working. ( as I mention in my previous mail) They used NAMD software and I am using gromacs. They sliced the receptor binding site and used the the solid support to the binding site and did simulation. So if I freeze the group is it will ok ?? Is it possible in gromacs to fix the residue on solid immobilized surface. If it is how to do it?? my question is How to decide which group are remove and which group should keep in simulation. thank you in advance Thank you for giving your valuable time and advice to me. With best wishes and regards, Rama david On Thu, Oct 4, 2012 at 6:11 PM, Thomas Evangelidis teva...@gmail.comwrote: I don't think AutoDock and Vina are suitable for peptide docking. I would first try the FlexPepDocking module of Rosetta which does ab initio folding of the peptide on the receptor, while moving the side-chains of the protein but leaves its backbone intact. Rosetta implements a knowledge-based scoring, which has been specifically designed for this task and is as fast as Vina or AutoDock. I would first do that and if I wouldn't get any reasonable results then I would move to MD starting from the top scored protein-peptide complexes created by Rosetta. Thomas On 4 October 2012 15:08, rama david ramadavidgr...@gmail.com wrote: Hi francesco, Thank you For reply. I did docking but the result are not so impressive. I used vina and autodock. I also did virtual screening in autodock but the result are not upto the mark. Is the freezing of group can affect my system?? How much efficiency I get by these work?? As these group are going to freeze in four simulation so if it affect one ligand it affect other ligand also. I read article that did the work like me , they sliced the binding residues and used the inert solid sphere to support binding residues instead of the freezing group other group. I think both way should have same effect..Am I right or wrong?? If you have any other way please suggest it.. With best wishes and regards Rama david On Thu, Oct 4, 2012 at 5:07 PM, francesco oteri francesco.ot...@gmail.com**wrote: Hi, as far as I know, freezing just set velocities to 0 so you gain nothing freezing atoms. By the way, have you tried docking? It takes into account multiple conformation and orientation of the peptide and, depending upon the implemented algorithm, also protein sidechain orientation. Francesco 2012/10/4 rama david ramadavidgr...@gmail.com thank you Justin for reply. I dont know about long range interactions. But as I freeze the group I think it will improve my computational speed. So is there any way to find out or decide which group should be freeze, and which group should affect my interaction most
Re: [gmx-users] Interaction study for peptide-receptor..
On 10/4/12 2:01 AM, rama david wrote: Hi gromacs Friends, I want to do peptide-receptor ( Protein) interaction study.Receptor consist a single chain. Peptide is made up of 4 amino acids. I know the interaction pattern of peptide and receptor. I plan to mutate single residue each at a time and run 4 simulation . So I will have the 4 different simulation that contain the mutated residues and the wild one. Then afterward from the interaction energy I want to select the peptide which is showing stronger interaction than others. As mention I know the binding site, If I freeze the remaining portion in receptor that not involved in binding , Is it going to affect my screening process ??? Potentially. Do you know that the binding interactions and the mutations will only perturb local residues? Do you know that there are no long-range motions to be considered? I think you gain very little by freezing portions of the system, and risk more than you gain. -Justin -- Justin A. Lemkul, Ph.D. Research Scientist Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
Re: [gmx-users] Interaction study for peptide-receptor..
thank you Justin for reply. I dont know about long range interactions. But as I freeze the group I think it will improve my computational speed. So is there any way to find out or decide which group should be freeze, and which group should affect my interaction most probably?? Should I do Essential Dynamics ??? or Principle component analysis ??? Would you suggest me any general protocol for such work?? Thank you in Advance With Best Wishes and regards. Rama David On Thu, Oct 4, 2012 at 3:57 PM, Justin Lemkul jalem...@vt.edu wrote: On 10/4/12 2:01 AM, rama david wrote: Hi gromacs Friends, I want to do peptide-receptor ( Protein) interaction study.Receptor consist a single chain. Peptide is made up of 4 amino acids. I know the interaction pattern of peptide and receptor. I plan to mutate single residue each at a time and run 4 simulation . So I will have the 4 different simulation that contain the mutated residues and the wild one. Then afterward from the interaction energy I want to select the peptide which is showing stronger interaction than others. As mention I know the binding site, If I freeze the remaining portion in receptor that not involved in binding , Is it going to affect my screening process ??? Potentially. Do you know that the binding interactions and the mutations will only perturb local residues? Do you know that there are no long-range motions to be considered? I think you gain very little by freezing portions of the system, and risk more than you gain. -Justin -- ==**== Justin A. Lemkul, Ph.D. Research Scientist Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.**vt.edu/Pages/Personal/justinhttp://www.bevanlab.biochem.vt.edu/Pages/Personal/justin ==**== -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/**mailman/listinfo/gmx-usershttp://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/** Support/Mailing_Lists/Searchhttp://www.gromacs.org/Support/Mailing_Lists/Searchbefore posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/**Support/Mailing_Listshttp://www.gromacs.org/Support/Mailing_Lists -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
Re: [gmx-users] Interaction study for peptide-receptor..
Hi, as far as I know, freezing just set velocities to 0 so you gain nothing freezing atoms. By the way, have you tried docking? It takes into account multiple conformation and orientation of the peptide and, depending upon the implemented algorithm, also protein sidechain orientation. Francesco 2012/10/4 rama david ramadavidgr...@gmail.com thank you Justin for reply. I dont know about long range interactions. But as I freeze the group I think it will improve my computational speed. So is there any way to find out or decide which group should be freeze, and which group should affect my interaction most probably?? Should I do Essential Dynamics ??? or Principle component analysis ??? Would you suggest me any general protocol for such work?? Thank you in Advance With Best Wishes and regards. Rama David On Thu, Oct 4, 2012 at 3:57 PM, Justin Lemkul jalem...@vt.edu wrote: On 10/4/12 2:01 AM, rama david wrote: Hi gromacs Friends, I want to do peptide-receptor ( Protein) interaction study.Receptor consist a single chain. Peptide is made up of 4 amino acids. I know the interaction pattern of peptide and receptor. I plan to mutate single residue each at a time and run 4 simulation . So I will have the 4 different simulation that contain the mutated residues and the wild one. Then afterward from the interaction energy I want to select the peptide which is showing stronger interaction than others. As mention I know the binding site, If I freeze the remaining portion in receptor that not involved in binding , Is it going to affect my screening process ??? Potentially. Do you know that the binding interactions and the mutations will only perturb local residues? Do you know that there are no long-range motions to be considered? I think you gain very little by freezing portions of the system, and risk more than you gain. -Justin -- ==**== Justin A. Lemkul, Ph.D. Research Scientist Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.**vt.edu/Pages/Personal/justin http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin ==**== -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/**mailman/listinfo/gmx-users http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/** Support/Mailing_Lists/Search http://www.gromacs.org/Support/Mailing_Lists/Searchbefore posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/**Support/Mailing_Lists http://www.gromacs.org/Support/Mailing_Lists -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists -- Cordiali saluti, Dr.Oteri Francesco -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
Re: [gmx-users] Interaction study for peptide-receptor..
Hi francesco, Thank you For reply. I did docking but the result are not so impressive. I used vina and autodock. I also did virtual screening in autodock but the result are not upto the mark. Is the freezing of group can affect my system?? How much efficiency I get by these work?? As these group are going to freeze in four simulation so if it affect one ligand it affect other ligand also. I read article that did the work like me , they sliced the binding residues and used the inert solid sphere to support binding residues instead of the freezing group other group. I think both way should have same effect..Am I right or wrong?? If you have any other way please suggest it.. With best wishes and regards Rama david On Thu, Oct 4, 2012 at 5:07 PM, francesco oteri francesco.ot...@gmail.comwrote: Hi, as far as I know, freezing just set velocities to 0 so you gain nothing freezing atoms. By the way, have you tried docking? It takes into account multiple conformation and orientation of the peptide and, depending upon the implemented algorithm, also protein sidechain orientation. Francesco 2012/10/4 rama david ramadavidgr...@gmail.com thank you Justin for reply. I dont know about long range interactions. But as I freeze the group I think it will improve my computational speed. So is there any way to find out or decide which group should be freeze, and which group should affect my interaction most probably?? Should I do Essential Dynamics ??? or Principle component analysis ??? Would you suggest me any general protocol for such work?? Thank you in Advance With Best Wishes and regards. Rama David On Thu, Oct 4, 2012 at 3:57 PM, Justin Lemkul jalem...@vt.edu wrote: On 10/4/12 2:01 AM, rama david wrote: Hi gromacs Friends, I want to do peptide-receptor ( Protein) interaction study.Receptor consist a single chain. Peptide is made up of 4 amino acids. I know the interaction pattern of peptide and receptor. I plan to mutate single residue each at a time and run 4 simulation . So I will have the 4 different simulation that contain the mutated residues and the wild one. Then afterward from the interaction energy I want to select the peptide which is showing stronger interaction than others. As mention I know the binding site, If I freeze the remaining portion in receptor that not involved in binding , Is it going to affect my screening process ??? Potentially. Do you know that the binding interactions and the mutations will only perturb local residues? Do you know that there are no long-range motions to be considered? I think you gain very little by freezing portions of the system, and risk more than you gain. -Justin -- ==**== Justin A. Lemkul, Ph.D. Research Scientist Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.**vt.edu/Pages/Personal/justin http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin ==**== -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/**mailman/listinfo/gmx-users http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/** Support/Mailing_Lists/Search http://www.gromacs.org/Support/Mailing_Lists/Searchbefore posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/**Support/Mailing_Lists http://www.gromacs.org/Support/Mailing_Lists -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists -- Cordiali saluti, Dr.Oteri Francesco -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read
Re: [gmx-users] Interaction study for peptide-receptor..
On 10/4/12 8:08 AM, rama david wrote: Hi francesco, Thank you For reply. I did docking but the result are not so impressive. I used vina and autodock. I also did virtual screening in autodock but the result are not upto the mark. Is the freezing of group can affect my system?? How much efficiency I get by these work?? You will not get any improvement in computational efficiency, and if you use NPT, you will get artifacts. One can potentially speed up a calculation using energygrp_excl, but that's layering assumptions upon assumptions, which I think is bad news. You've said you don't know if long-range interactions play a role. That, to me, means you absolutely cannot justify any sort of freezing. The fact that docking did not produce very good results is unsurprising. The largely rigid treatment of proteins in docking leaves much to be desired. This is yet another argument against freezing parts of your protein - if docking did not produce good results, why would you expect a mostly frozen MD system to perform much better? As these group are going to freeze in four simulation so if it affect one ligand it affect other ligand also. I read article that did the work like me , they sliced the binding residues and used the inert solid sphere to support binding residues instead of the freezing group other group. I think both way should have same effect..Am I right or wrong?? I don't really understand what it is the other group did, aside from perhaps modeling a subsystem. Still, I don't think such lengths are necessary or inherently beneficial. If you have any other way please suggest it.. I see no reason not to treat this system with normal MD protocols. -Justin -- Justin A. Lemkul, Ph.D. Research Scientist Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
Re: [gmx-users] Interaction study for peptide-receptor..
2012/10/4 rama david ramadavidgr...@gmail.com Hi francesco, Thank you For reply. I did docking but the result are not so impressive. What does it mean not so impressive? I mean, do you have experimental data and the comparison with docking doesn't agree with experiments? Have you generated a sufficient number of complexes (say 100 or more)? I used vina and autodock. I also did virtual screening in autodock but the result are not upto the mark. Is the freezing of group can affect my system?? How much efficiency I get by these work?? It will change a lot the dynamics of your system and I don't think calculations will be more efficient! As these group are going to freeze in four simulation so if it affect one ligand it affect other ligand also. I read article that did the work like me , they sliced the binding residues and used the inert solid sphere to support binding residues instead of the freezing group other group. I think both way should have same effect..Am I right or wrong?? If you have any other way please suggest it.. If you already have docking complexes, you can pick up one complex for each peptide, to run an MD, or Free Energy calculations. It strongly depends by the experimentale data you have and what is the target of your work. With best wishes and regards Rama david On Thu, Oct 4, 2012 at 5:07 PM, francesco oteri francesco.ot...@gmail.comwrote: Hi, as far as I know, freezing just set velocities to 0 so you gain nothing freezing atoms. By the way, have you tried docking? It takes into account multiple conformation and orientation of the peptide and, depending upon the implemented algorithm, also protein sidechain orientation. Francesco 2012/10/4 rama david ramadavidgr...@gmail.com thank you Justin for reply. I dont know about long range interactions. But as I freeze the group I think it will improve my computational speed. So is there any way to find out or decide which group should be freeze, and which group should affect my interaction most probably?? Should I do Essential Dynamics ??? or Principle component analysis ??? Would you suggest me any general protocol for such work?? Thank you in Advance With Best Wishes and regards. Rama David On Thu, Oct 4, 2012 at 3:57 PM, Justin Lemkul jalem...@vt.edu wrote: On 10/4/12 2:01 AM, rama david wrote: Hi gromacs Friends, I want to do peptide-receptor ( Protein) interaction study.Receptor consist a single chain. Peptide is made up of 4 amino acids. I know the interaction pattern of peptide and receptor. I plan to mutate single residue each at a time and run 4 simulation . So I will have the 4 different simulation that contain the mutated residues and the wild one. Then afterward from the interaction energy I want to select the peptide which is showing stronger interaction than others. As mention I know the binding site, If I freeze the remaining portion in receptor that not involved in binding , Is it going to affect my screening process ??? Potentially. Do you know that the binding interactions and the mutations will only perturb local residues? Do you know that there are no long-range motions to be considered? I think you gain very little by freezing portions of the system, and risk more than you gain. -Justin -- ==**== Justin A. Lemkul, Ph.D. Research Scientist Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.**vt.edu/Pages/Personal/justin http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin ==**== -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/**mailman/listinfo/gmx-users http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/** Support/Mailing_Lists/Search http://www.gromacs.org/Support/Mailing_Lists/Searchbefore posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/**Support/Mailing_Lists http://www.gromacs.org/Support/Mailing_Lists -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists -- Cordiali saluti, Dr.Oteri Francesco -- gmx-users
Re: [gmx-users] Interaction study for peptide-receptor..
Thank you justin and franscisco, I have practical data that claim that only a particular residue that is c terminal residue is involve in binding. but when I generate the docking data other residues most of the time comes to play. I know the binding of natural ligand ( peptide ) and the position. so I think if I mutate only these residue and simulate the system I will get the structure that is more active. In natural ligand the C terminal is playing important role. With simulation i will find interaction energy. That will tell me about binding affinity ( Hope so ) These is my basic idea. Is any other way to do the same thing.. With best wishes and regards Rama David On Thu, Oct 4, 2012 at 5:47 PM, francesco oteri francesco.ot...@gmail.comwrote: 2012/10/4 rama david ramadavidgr...@gmail.com Hi francesco, Thank you For reply. I did docking but the result are not so impressive. What does it mean not so impressive? I mean, do you have experimental data and the comparison with docking doesn't agree with experiments? Have you generated a sufficient number of complexes (say 100 or more)? I used vina and autodock. I also did virtual screening in autodock but the result are not upto the mark. Is the freezing of group can affect my system?? How much efficiency I get by these work?? It will change a lot the dynamics of your system and I don't think calculations will be more efficient! As these group are going to freeze in four simulation so if it affect one ligand it affect other ligand also. I read article that did the work like me , they sliced the binding residues and used the inert solid sphere to support binding residues instead of the freezing group other group. I think both way should have same effect..Am I right or wrong?? If you have any other way please suggest it.. If you already have docking complexes, you can pick up one complex for each peptide, to run an MD, or Free Energy calculations. It strongly depends by the experimentale data you have and what is the target of your work. With best wishes and regards Rama david On Thu, Oct 4, 2012 at 5:07 PM, francesco oteri francesco.ot...@gmail.comwrote: Hi, as far as I know, freezing just set velocities to 0 so you gain nothing freezing atoms. By the way, have you tried docking? It takes into account multiple conformation and orientation of the peptide and, depending upon the implemented algorithm, also protein sidechain orientation. Francesco 2012/10/4 rama david ramadavidgr...@gmail.com thank you Justin for reply. I dont know about long range interactions. But as I freeze the group I think it will improve my computational speed. So is there any way to find out or decide which group should be freeze, and which group should affect my interaction most probably?? Should I do Essential Dynamics ??? or Principle component analysis ??? Would you suggest me any general protocol for such work?? Thank you in Advance With Best Wishes and regards. Rama David On Thu, Oct 4, 2012 at 3:57 PM, Justin Lemkul jalem...@vt.edu wrote: On 10/4/12 2:01 AM, rama david wrote: Hi gromacs Friends, I want to do peptide-receptor ( Protein) interaction study.Receptor consist a single chain. Peptide is made up of 4 amino acids. I know the interaction pattern of peptide and receptor. I plan to mutate single residue each at a time and run 4 simulation . So I will have the 4 different simulation that contain the mutated residues and the wild one. Then afterward from the interaction energy I want to select the peptide which is showing stronger interaction than others. As mention I know the binding site, If I freeze the remaining portion in receptor that not involved in binding , Is it going to affect my screening process ??? Potentially. Do you know that the binding interactions and the mutations will only perturb local residues? Do you know that there are no long-range motions to be considered? I think you gain very little by freezing portions of the system, and risk more than you gain. -Justin -- ==**== Justin A. Lemkul, Ph.D. Research Scientist Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.**vt.edu/Pages/Personal/justin http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin ==**== -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/**mailman/listinfo/gmx-users
Re: [gmx-users] Interaction study for peptide-receptor..
On 10/4/12 8:40 AM, rama david wrote: Thank you justin and franscisco, I have practical data that claim that only a particular residue that is c terminal residue is involve in binding. but when I generate the docking data other residues most of the time comes to play. I know the binding of natural ligand ( peptide ) and the position. so I think if I mutate only these residue and simulate the system I will get the structure that is more active. In natural ligand the C terminal is playing important role. With simulation i will find interaction energy. Interaction energy is a very vague term that people often use fairly erroneously to justify their findings. Force fields are not necessarily guaranteed to produce anything meaningful from the sum of nonbonded terms. That will tell me about binding affinity ( Hope so ) More sophisticated free energy calculations would be necessary to determine binding affinity or free energy of binding. -Justin -- Justin A. Lemkul, Ph.D. Research Scientist Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
Re: [gmx-users] Interaction study for peptide-receptor..
I don't think AutoDock and Vina are suitable for peptide docking. I would first try the FlexPepDocking module of Rosetta which does ab initio folding of the peptide on the receptor, while moving the side-chains of the protein but leaves its backbone intact. Rosetta implements a knowledge-based scoring, which has been specifically designed for this task and is as fast as Vina or AutoDock. I would first do that and if I wouldn't get any reasonable results then I would move to MD starting from the top scored protein-peptide complexes created by Rosetta. Thomas On 4 October 2012 15:08, rama david ramadavidgr...@gmail.com wrote: Hi francesco, Thank you For reply. I did docking but the result are not so impressive. I used vina and autodock. I also did virtual screening in autodock but the result are not upto the mark. Is the freezing of group can affect my system?? How much efficiency I get by these work?? As these group are going to freeze in four simulation so if it affect one ligand it affect other ligand also. I read article that did the work like me , they sliced the binding residues and used the inert solid sphere to support binding residues instead of the freezing group other group. I think both way should have same effect..Am I right or wrong?? If you have any other way please suggest it.. With best wishes and regards Rama david On Thu, Oct 4, 2012 at 5:07 PM, francesco oteri francesco.ot...@gmail.comwrote: Hi, as far as I know, freezing just set velocities to 0 so you gain nothing freezing atoms. By the way, have you tried docking? It takes into account multiple conformation and orientation of the peptide and, depending upon the implemented algorithm, also protein sidechain orientation. Francesco 2012/10/4 rama david ramadavidgr...@gmail.com thank you Justin for reply. I dont know about long range interactions. But as I freeze the group I think it will improve my computational speed. So is there any way to find out or decide which group should be freeze, and which group should affect my interaction most probably?? Should I do Essential Dynamics ??? or Principle component analysis ??? Would you suggest me any general protocol for such work?? Thank you in Advance With Best Wishes and regards. Rama David On Thu, Oct 4, 2012 at 3:57 PM, Justin Lemkul jalem...@vt.edu wrote: On 10/4/12 2:01 AM, rama david wrote: Hi gromacs Friends, I want to do peptide-receptor ( Protein) interaction study.Receptor consist a single chain. Peptide is made up of 4 amino acids. I know the interaction pattern of peptide and receptor. I plan to mutate single residue each at a time and run 4 simulation . So I will have the 4 different simulation that contain the mutated residues and the wild one. Then afterward from the interaction energy I want to select the peptide which is showing stronger interaction than others. As mention I know the binding site, If I freeze the remaining portion in receptor that not involved in binding , Is it going to affect my screening process ??? Potentially. Do you know that the binding interactions and the mutations will only perturb local residues? Do you know that there are no long-range motions to be considered? I think you gain very little by freezing portions of the system, and risk more than you gain. -Justin -- ==**== Justin A. Lemkul, Ph.D. Research Scientist Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.**vt.edu/Pages/Personal/justin http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin ==**== -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/**mailman/listinfo/gmx-users http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/** Support/Mailing_Lists/Search http://www.gromacs.org/Support/Mailing_Lists/Searchbefore posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/**Support/Mailing_Lists http://www.gromacs.org/Support/Mailing_Lists -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists -- Cordiali
Re: [gmx-users] Interaction study for peptide-receptor..
Thank you for reply, I read the recently published article in Biochemistry. They worked on the same receptor that I am working. ( as I mention in my previous mail) They used NAMD software and I am using gromacs. They sliced the receptor binding site and used the the solid support to the binding site and did simulation. So if I freeze the group is it will ok ?? Is it possible in gromacs to fix the residue on solid immobilized surface. If it is how to do it?? my question is How to decide which group are remove and which group should keep in simulation. thank you in advance Thank you for giving your valuable time and advice to me. With best wishes and regards, Rama david On Thu, Oct 4, 2012 at 6:11 PM, Thomas Evangelidis teva...@gmail.comwrote: I don't think AutoDock and Vina are suitable for peptide docking. I would first try the FlexPepDocking module of Rosetta which does ab initio folding of the peptide on the receptor, while moving the side-chains of the protein but leaves its backbone intact. Rosetta implements a knowledge-based scoring, which has been specifically designed for this task and is as fast as Vina or AutoDock. I would first do that and if I wouldn't get any reasonable results then I would move to MD starting from the top scored protein-peptide complexes created by Rosetta. Thomas On 4 October 2012 15:08, rama david ramadavidgr...@gmail.com wrote: Hi francesco, Thank you For reply. I did docking but the result are not so impressive. I used vina and autodock. I also did virtual screening in autodock but the result are not upto the mark. Is the freezing of group can affect my system?? How much efficiency I get by these work?? As these group are going to freeze in four simulation so if it affect one ligand it affect other ligand also. I read article that did the work like me , they sliced the binding residues and used the inert solid sphere to support binding residues instead of the freezing group other group. I think both way should have same effect..Am I right or wrong?? If you have any other way please suggest it.. With best wishes and regards Rama david On Thu, Oct 4, 2012 at 5:07 PM, francesco oteri francesco.ot...@gmail.comwrote: Hi, as far as I know, freezing just set velocities to 0 so you gain nothing freezing atoms. By the way, have you tried docking? It takes into account multiple conformation and orientation of the peptide and, depending upon the implemented algorithm, also protein sidechain orientation. Francesco 2012/10/4 rama david ramadavidgr...@gmail.com thank you Justin for reply. I dont know about long range interactions. But as I freeze the group I think it will improve my computational speed. So is there any way to find out or decide which group should be freeze, and which group should affect my interaction most probably?? Should I do Essential Dynamics ??? or Principle component analysis ??? Would you suggest me any general protocol for such work?? Thank you in Advance With Best Wishes and regards. Rama David On Thu, Oct 4, 2012 at 3:57 PM, Justin Lemkul jalem...@vt.edu wrote: On 10/4/12 2:01 AM, rama david wrote: Hi gromacs Friends, I want to do peptide-receptor ( Protein) interaction study.Receptor consist a single chain. Peptide is made up of 4 amino acids. I know the interaction pattern of peptide and receptor. I plan to mutate single residue each at a time and run 4 simulation . So I will have the 4 different simulation that contain the mutated residues and the wild one. Then afterward from the interaction energy I want to select the peptide which is showing stronger interaction than others. As mention I know the binding site, If I freeze the remaining portion in receptor that not involved in binding , Is it going to affect my screening process ??? Potentially. Do you know that the binding interactions and the mutations will only perturb local residues? Do you know that there are no long-range motions to be considered? I think you gain very little by freezing portions of the system, and risk more than you gain. -Justin -- ==**== Justin A. Lemkul, Ph.D. Research Scientist Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.**vt.edu/Pages/Personal/justin http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin ==**== -- gmx-users mailing listgmx-users@gromacs.org
Re: [gmx-users] Interaction study for peptide-receptor..
On 10/4/12 9:16 AM, rama david wrote: Thank you for reply, I read the recently published article in Biochemistry. They worked on the same receptor that I am working. ( as I mention in my previous mail) They used NAMD software and I am using gromacs. They sliced the receptor binding site and used the the solid support to the binding site and did simulation. So if I freeze the group is it will ok ?? I've already stated my opinion on this matter, so I won't state it again. I will not try to pre-judge a study I have not read (regarding the solid support) but it seems to me that if you are analyzing the binding of a peptide to a protein, that is fairly straightforward MD without anything fancy. Is it possible in gromacs to fix the residue on solid immobilized surface. If it is how to do it?? Build a surface, create a merged moleculetype, and define bonds between protein atoms and surface atoms. This all sounds like a ridiculous amount of work. my question is How to decide which group are remove and which group should keep in simulation. IMHO, it's not worth doing in this way. -Justin -- Justin A. Lemkul, Ph.D. Research Scientist Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
