[gmx-users] Docking validation
Dear Justin I docked a ligand to a hetrodimer protein, I know the approximate position of the ligand but I don't know whether or not the docked ligand is relaxed in the binding site or is it taken the proper orientation? I run the ligand-protein complex for 5ns MD by using charmm force field and applied position restraint and constraint forall bonds (ligand parameters obtained from swissparam server). Should I apply restraint and constraint? Or I have to remove them for better flexibility if its yes how should I remove them? And will the simulation be correct if I remove them? Could I mark some residue of binding site to force them to interact with the ligand? How? To understand whether simulation could or not predict the correct position of a ligand, I docked another ligand to its binding site which their crystallographic structure had been provided before, I used the worst docking pose for performing the same MDS, at last I compared the positions of two ligands (crystallographic and simulated), simulation hardly changed the position of the ligand after 5ns although its position energetically was wrong (based on docking and crystallographic pdb file). If MDS continue for several µs will the ligand find the correct position and orientation? Given that I couldn't meet such a MDS how can I speed up this simulation? Will it be useful to mark some residues for interaction or put the ligand near the binding site by dragging or do a flexible docking? Sincerely M.Javaheri -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
[gmx-users] tip3p
Hi All I have tip3p water potential parameters from 3 different sources and they differ quite substantially. I tried finding answer on the web or manual, but no success. Following lists all the three sources and bond potential force constant (kb) value, in bracket as an example of how values differ in all the three sources. 1. From the article: Neria, E.; Fischer, S.; Karplus, M. J. Chem. Phys. 1996, 105, 1902. (kb= 450 kcal/(mol.A02)), where A0 is angstrom. ( in Gromacs units, kb=188280 kcal/(mol.A02)) 2. From tip3p files in forcefield directories in gromacs/4.6.3/share/gromacs/top (502416.0 kJ/(mol.nm2) 3. That used by acpype tool while converting amber input files to gromacs input files.( 462750.4 kJ/(mol.nm2)) 2 and 3 force constant units should conform to Gromacs, so kJ and nm. It's very confusing, surprising and disappointing why these three values differ so much. What is the correct value and why? I really appreciate your response. Thanks Chetan -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] tip3p
On Sun, Mar 9, 2014 at 1:00 PM, Chetan Mahajan chetanv...@gmail.com wrote: Hi All I have tip3p water potential parameters from 3 different sources and they differ quite substantially. I tried finding answer on the web or manual, but no success. Following lists all the three sources and bond potential force constant (kb) value, in bracket as an example of how values differ in all the three sources. 1. From the article: Neria, E.; Fischer, S.; Karplus, M. J. Chem. Phys. 1996, 105, 1902. (kb= 450 kcal/(mol.A02)), where A0 is angstrom. ( in Gromacs units, kb=188280 kcal/(mol.A02)) This is not the TIP3P citation (see gromacs manual), and as you can see in the penultimate paragraph, it does not even use the standard TIP3P. 2. From tip3p files in forcefield directories in gromacs/4.6.3/share/gromacs/top (502416.0 kJ/(mol.nm2) This agrees with Jorgensen 1983 3. That used by acpype tool while converting amber input files to gromacs input files.( 462750.4 kJ/(mol.nm2)) No idea where this is from or what it is doing, but presumably reading the documentation or code will be a good start! :-) Mark 2 and 3 force constant units should conform to Gromacs, so kJ and nm. It's very confusing, surprising and disappointing why these three values differ so much. What is the correct value and why? I really appreciate your response. Thanks Chetan -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] CHARMM36 force field available for GROMACS
On 3/9/14, 6:28 AM, jim wrote: I'm confused about the existence of H5'1 and H5'2 atom names in the RNA nucleotides (in merge.rtp). I thought all atom names followed the CHARMM 36 atom name convention. Particularly, why do atoms H2' and H2'' correspond to the latter, while H5'1 and H5'2 carry the same name as the Gromacs convention? At the same time, in [bonds] H5' and H5'' are used instead of H5'1 and H5'2. I suspect H5'1 and H5'2 should have been H5' and H5''. On the other hand, I assume H5'1 and H5'2 are correct for the DNA since there is a correspondence with H2'1 and H2'2. What we tried to do was make the fewest changes possible to CHARMM nomenclature, while still playing nice the the Gromacs .hdb and .tdb machinery. You are correct in noting the error in the [bonds] involving H5' and H5'' for RNA - I will see that this problem is fixed in our next release. Bonds involving H5' and H5'' in RNA residues should indeed be changed to the H5'1 and H5'2 nomenclature. The H2' and H2'' used in RNA are correct. Since H2'' is bonded to C2' and H2' is bonded to O2', there is no issue in .hdb generation that leads to any problem, so those names were left untouched. Since, in DNA, H2' and H2'' are both bonded to C2', they needed to be renamed. Please let me know if you spot anything else that is unusual or incorrect. -Justin -- == Justin A. Lemkul, Ph.D. Ruth L. Kirschstein NRSA Postdoctoral Fellow Department of Pharmaceutical Sciences School of Pharmacy Health Sciences Facility II, Room 601 University of Maryland, Baltimore 20 Penn St. Baltimore, MD 21201 jalem...@outerbanks.umaryland.edu | (410) 706-7441 http://mackerell.umaryland.edu/~jalemkul == -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] tip3p
Hi Mark, Thanks for the reply. Now, 1983 article by Jorgensen gives parameters for rigid tip3p, whereas I am seeking that for flexible tip3p. Force constant is not mentioned in 1983 article by Jorgensen. The article that I cited in #1 point below gives these parameters for modified tip3p. I do not understand why these are different from those in tip3p files in gromacs installed. Is there any other article describing flexible tip3p parameters? Thanks Chetan On Sun, Mar 9, 2014 at 7:33 AM, Mark Abraham mark.j.abra...@gmail.comwrote: On Sun, Mar 9, 2014 at 1:00 PM, Chetan Mahajan chetanv...@gmail.com wrote: Hi All I have tip3p water potential parameters from 3 different sources and they differ quite substantially. I tried finding answer on the web or manual, but no success. Following lists all the three sources and bond potential force constant (kb) value, in bracket as an example of how values differ in all the three sources. 1. From the article: Neria, E.; Fischer, S.; Karplus, M. J. Chem. Phys. 1996, 105, 1902. (kb= 450 kcal/(mol.A02)), where A0 is angstrom. ( in Gromacs units, kb=188280 kcal/(mol.A02)) This is not the TIP3P citation (see gromacs manual), and as you can see in the penultimate paragraph, it does not even use the standard TIP3P. 2. From tip3p files in forcefield directories in gromacs/4.6.3/share/gromacs/top (502416.0 kJ/(mol.nm2) This agrees with Jorgensen 1983 3. That used by acpype tool while converting amber input files to gromacs input files.( 462750.4 kJ/(mol.nm2)) No idea where this is from or what it is doing, but presumably reading the documentation or code will be a good start! :-) Mark 2 and 3 force constant units should conform to Gromacs, so kJ and nm. It's very confusing, surprising and disappointing why these three values differ so much. What is the correct value and why? I really appreciate your response. Thanks Chetan -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] CHARMM36 force field available for GROMACS
Thanks for the clarification. *Bonds involving H5' and H5'' in RNA residues should indeed be changed to the H5'1 and H5'2 nomenclature.* Even though H5' and H5'' are connected to the same atom, what would be the problem to keep these H atom names H5' and H5'' instead of changing them to H5'1 and H5'2? Also, what is the significance of the -O3' P bond listed in the [bonds] of the RNA nucleotides in the previous CHARMM 27 FF? It is absent in CHARMM 36. Thanks. On Sun, Mar 9, 2014 at 6:34 AM, Justin Lemkul jalem...@vt.edu wrote: On 3/9/14, 6:28 AM, jim wrote: I'm confused about the existence of H5'1 and H5'2 atom names in the RNA nucleotides (in merge.rtp). I thought all atom names followed the CHARMM 36 atom name convention. Particularly, why do atoms H2' and H2'' correspond to the latter, while H5'1 and H5'2 carry the same name as the Gromacs convention? At the same time, in [bonds] H5' and H5'' are used instead of H5'1 and H5'2. I suspect H5'1 and H5'2 should have been H5' and H5''. On the other hand, I assume H5'1 and H5'2 are correct for the DNA since there is a correspondence with H2'1 and H2'2. What we tried to do was make the fewest changes possible to CHARMM nomenclature, while still playing nice the the Gromacs .hdb and .tdb machinery. You are correct in noting the error in the [bonds] involving H5' and H5'' for RNA - I will see that this problem is fixed in our next release. Bonds involving H5' and H5'' in RNA residues should indeed be changed to the H5'1 and H5'2 nomenclature. The H2' and H2'' used in RNA are correct. Since H2'' is bonded to C2' and H2' is bonded to O2', there is no issue in .hdb generation that leads to any problem, so those names were left untouched. Since, in DNA, H2' and H2'' are both bonded to C2', they needed to be renamed. Please let me know if you spot anything else that is unusual or incorrect. -Justin -- == Justin A. Lemkul, Ph.D. Ruth L. Kirschstein NRSA Postdoctoral Fellow Department of Pharmaceutical Sciences School of Pharmacy Health Sciences Facility II, Room 601 University of Maryland, Baltimore 20 Penn St. Baltimore, MD 21201 jalem...@outerbanks.umaryland.edu | (410) 706-7441 http://mackerell.umaryland.edu/~jalemkul == -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/ Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] CHARMM36 force field available for GROMACS
Thanks, but I'll have to ask you something again. :) On Sun, Mar 9, 2014 at 5:00 PM, Justin Lemkul jalem...@vt.edu wrote: On 3/9/14, 7:23 PM, Jim wrote: Thanks for the clarification. *Bonds involving H5' and H5'' in RNA residues should indeed be changed to the H5'1 and H5'2 nomenclature.* Even though H5' and H5'' are connected to the same atom, what would be the problem to keep these H atom names H5' and H5'' instead of changing them to H5'1 and H5'2? In principle, no, the CHARMM-specific names should work fine, but only if you add corresponding entries in the merged.arn file to translate between CHARMM and Gromacs nomenclature. We made the naming change to interface smoothly with the Gromacs hydrogen-generation (.hdb) mechanism. If you have a coordinate file that complies with CHARMM naming, i.e. from CHARMM-GUI, then simple sed statements take care of any issues. Although this makes sense, it also brings other questions. I don't really understand the significance of the *hdb file - isn't its sole purpose to add hydrogens to coordinates that don't have all hydrogens? Second, what kind of a file is merged.am? I've never seen such a file... Third, if the H2' and H2'' of the RNA nucleotides do not correspond to the Gromacs nomenclature as well, then where exactly is their CHARMM-Gromacs conversion taken care of? In other words, if I use H5' and H5'' names instead of H5'1 and H5'2, isn't this equivalent to using the H2' and H2'' names instead of H2'1 and H2'2 in terms of translating between nomenclatures? Basically, I have a CHARMM 36 solvated file with all necessary hydrogens generated with CHARMM, do some rotation (for PBC matching) and then something like this: cat $pdbfile | sed 's/TIP3/SOL /' | sed 's/ OH2 SOL/ OW SOL/' | sed 's/ H1 SOL/ HW1 SOL/' | sed 's/ H2 SOL/ HW2 SOL/' | sed 's/ SOD SOD/ NA NA /g ' | sed 's/ CLA CLA/ CL CL /g' I don't change the names of any other atom or residue. I use H5' and H5''. I change ADE, GUA, CYT, URA to use the H5' and H5'' atom names in the merge.rtp as well. I don't touch the [bonds] because they already use these atom names. I generate a topology and *.gro with pdb2gmx. It looks like this (e.g. for one residue): [ atoms ] ; nr type resnr residue atom cgnr charge mass typeB chargeB massB ; residue 17 GUA rtp GUA q -0.5 1ON5 17GUAO5' 1 -0.6615.9994 ; qtot -0.66 2HN5 17GUAH5T 2 0.43 1.008 ; qtot -0.23 3 CN8B 17GUAC5' 3 0.05 12.011 ; qtot -0.18 4HN8 17GUAH5' 4 0.09 1.008 ; qtot -0.09 5HN8 17GUA H5'' 5 0.09 1.008 ; qtot 0 6CN7 17GUAC4' 6 0.16 12.011 ; qtot 0.16 7HN7 17GUAH4' 7 0.09 1.008 ; qtot 0.25 8 ON6B 17GUAO4' 8 -0.515.9994 ; qtot -0.25 9 CN7B 17GUAC1' 9 0.16 12.011 ; qtot -0.09 10HN7 17GUAH1' 10 0.09 1.008 ; qtot 0 11 NN2B 17GUA N9 11 -0.02 14.007 ; qtot -0.02 12CN5 17GUA C4 12 0.26 12.011 ; qtot 0.24 13NN1 17GUA N2 13 -0.68 14.007 ; qtot -0.44 14HN1 17GUAH21 14 0.32 1.008 ; qtot -0.12 15HN1 17GUAH22 15 0.35 1.008 ; qtot 0.23 16 NN3G 17GUA N3 16 -0.74 14.007 ; qtot -0.51 17CN2 17GUA C2 17 0.75 12.011 ; qtot 0.24 18 NN2G 17GUA N1 18 -0.34 14.007 ; qtot -0.1 19HN2 17GUA H1 19 0.26 1.008 ; qtot 0.16 20CN1 17GUA C6 20 0.54 12.011 ; qtot 0.7 21ON1 17GUA O6 21 -0.5115.9994 ; qtot 0.19 22 CN5G 17GUA C5 22 0 12.011 ; qtot 0.19 23NN4 17GUA N7 23 -0.6 14.007 ; qtot -0.41 24CN4 17GUA C8 24 0.25 12.011 ; qtot -0.16 25HN3 17GUA H8 25 0.16 1.008 ; qtot 0 26 CN7B 17GUAC2' 26 0.14 12.011 ; qtot 0.14 27HN7 17GUA H2'' 27 0.09 1.008 ; qtot 0.23 28ON5 17GUAO2' 28 -0.6615.9994 ; qtot -0.43 29HN5 17GUAH2' 29 0.43 1.008 ; qtot 0 30CN7 17GUAC3' 30 0.01 12.011 ; qtot 0.01 31HN7 17GUAH3' 31 0.09 1.008 ; qtot 0.1 32ON2 17GUAO3' 32
