Re: [gmx-users] umbrella sampling and PMF calculation by using pull-geometry=direction in gromacs 5.0.4
I see your confusion now. The PMF is actually defined as dG(x) + C, where C is some unknown constant. Therefore, in the left figure, you have dG_a(x) + C_a and on the right you have dG_b(x) + C_b, so if the profiles have the same shape then the PMFs can be identical if C_a is different from C_b. Subtract 80 from all y-values in the left plot and it will look more like the right plot. For some reason, your WHAM program has placed the minimum at zero in one plot and the maximum at zero in the other plot. I'm guessing the value at minimum x gets set to zero. Chris. From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se gromacs.org_gmx-users-boun...@maillist.sys.kth.se on behalf of mahender singh pharmbioc...@live.com Sent: 04 May 2015 21:50 To: gromacs user_list Subject: Re: [gmx-users] umbrella sampling and PMF calculation by using pull-geometry=direction in gromacs 5.0.4 Thanks for the advice I will do this exercise with other molecule and will let you know the results. but, why i was confused is because in one PMF curve all the free energy values are on the positive side where as the other has all free energy values on the negative side. do these signs are not important or there is something else. As What I understand is that if the free energy of the drug increases when going to the center of the bilayer, this drug cannot passively diffuse across the membrane (thermodynamically unfavored ). I will try to go through more literature on this topic to understand this concept in more detail. thanks you with regards Mahender Singh -- 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] umbrella sampling and PMF calculation by using pull-geometry=direction in gromacs 5.0.4
Can you walk me through that image and tell me what you see that is different from what you expect? I see a maximum at z=0 in both cases (I presume z=0 is the bilayer center). I'm happy to continue guessing, but you are really best to take something like hexane in a simplified bilayer and do a test. If you don't see something like this: http://pubs.acs.org/doi/abs/10.1021/ja0535099 then you've got a problem. From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se gromacs.org_gmx-users-boun...@maillist.sys.kth.se on behalf of mahender singh pharmbioc...@live.com Sent: 04 May 2015 00:57 To: gromacs user_list Subject: Re: [gmx-users] umbrella sampling and PMF calculation by using pull-geometry=direction in gromacs 5.0.4 Thanks Chris for your help I am using Isoniazid drug and the membrane model is a mixture of different lipid types (POPE,POPC,POPI,POPS,cholesterol) in a ratio mimicking the plasma membrane more closely as compared to the simple single lipid type membrane model. I have attached the PMF plot (attachment, shared link), and sorry for the partial PMF graph as one can see sampling is not sufficient , as I stopped further umbrella sampling, because of strange results. One is made by using pull-geometry=distance, free, energy on the negative side (limited to the one leaflet, as distance between two group become zero drug will not move onto the other side) and other by using pull-geometry=direction for the same drug i.e. isoniazid, free energy on the positive side. https://onedrive.live.com/redir?resid=DA38458F80BE68E9!192authkey=!ACGecvNH6tPzIloithint=folder%2c All the parameters were same except pull-geomerty i.e distance or direction. But free energy graph is completely opposite in both the cases and this should not be , as I thinks. As for the same drug free energy profile should not be completely opposite for the one drug, so may be I making some mistake in the umbrella sampling parameters. Can you provide me some suggestion on this topic. Thanks in advance for help. with regards Mahender Singh Hello good morning to all I did steered md simulation by using following code ;pull code pull= umbrella pull_geometry= direction pull_dim= N N Y pull_coord1_vec=0 0 1 pull_start= yes pull_ngroups=2 pull-ncoords=1 pull_coord1_groups= 1 2 pull_group1_name= NPROT_ref pull_group2_name= LIG pull_coord1_rate= 0.004; 0.004 nm per ps = 4 nm per ns pull_coord1_k= 1000; kJ mol^-1 nm^-2 pull_nstxout= 500; every 1 ps pull_nstfout= 500; every 1 ps And then used these results of SMD for umbrella sampling (total umbrella window =30 across the membrane) by using following code pull= umbrella pull_geometry= direction pull_dim= N N Y pull_coord1_vec=0 0 1 pull_start= yes pull_ngroups=2 pull-ncoords=1 pull_coord1_groups= 1 2 pull_group1_name= NPROT_ref pull_group2_name= LIG pull_coord1_rate= 0.0 pull_coord1_k= 1000; kJ mol^-1 nm^-2 pull_nstxout= 500; every 1 ps pull_nstfout= 500; every 1 ps In my case, I am moving a molecule from -z to +z across the membrane. So I used pull-geometry=direction in gromacs 5.0.4 (as per gromacs site= http://www.gromacs.org/Documentation/How-tos/Potential_of_Mean_Force), as I cannot use pull-geimetry=distance. Every thing completed correctly (seems to me), but when I used gmx wham on the pullf.xvg files, PMF profile was on the positive side. PMF increased from 0 (bulk water) to 60 at the center of the membrane and than again decreased to the 0 (bulk water on the other side). I all the literature, PMF values for the molecule crossing a membrane is on the negative side and minimum at the center. I am confused about the result. Did I do something wrong with the parameters or understanding the PMF curve wrongly. can any one give their suggestion on this. thanks in advance of user time and help. with regards Mahender Singh -- 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. -- Message: 3 Date: Sun, 3 May 2015 12:25:01 + From: Christopher Neale chris.ne...@alum.utoronto.ca To: gmx-us...@gromacs.org gmx-us...@gromacs.org Subject: Re: [gmx-users] umbrella sampling and PMF calculation by using pull-geometry=direction in gromacs 5.0.4 Message-ID: 1430655898617.32...@alum.utoronto.ca Content-Type: text/plain; charset=iso-8859-1 Better yet, repeat something that is already out there in the literature.
Re: [gmx-users] umbrella sampling and PMF calculation by using pull-geometry=direction in gromacs 5.0.4
Better yet, repeat something that is already out there in the literature. PMFs for water, lipids, and some amino acid side chains across the bilayer have been tested extensively. Chris. From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se gromacs.org_gmx-users-boun...@maillist.sys.kth.se on behalf of mahender singh pharmbioc...@live.com Sent: 03 May 2015 01:07 To: gromacs user_list Subject: [gmx-users] umbrella sampling and PMF calculation by using pull-geometry=direction in gromacs 5.0.4 Hello good morning to all I did steered md simulation by using following code ;pull code pull= umbrella pull_geometry= direction pull_dim= N N Y pull_coord1_vec=0 0 1 pull_start= yes pull_ngroups=2 pull-ncoords=1 pull_coord1_groups= 1 2 pull_group1_name= NPROT_ref pull_group2_name= LIG pull_coord1_rate= 0.004; 0.004 nm per ps = 4 nm per ns pull_coord1_k= 1000; kJ mol^-1 nm^-2 pull_nstxout= 500; every 1 ps pull_nstfout= 500; every 1 ps And then used these results of SMD for umbrella sampling (total umbrella window =30 across the membrane) by using following code pull= umbrella pull_geometry= direction pull_dim= N N Y pull_coord1_vec=0 0 1 pull_start= yes pull_ngroups=2 pull-ncoords=1 pull_coord1_groups= 1 2 pull_group1_name= NPROT_ref pull_group2_name= LIG pull_coord1_rate= 0.0 pull_coord1_k= 1000; kJ mol^-1 nm^-2 pull_nstxout= 500; every 1 ps pull_nstfout= 500; every 1 ps In my case, I am moving a molecule from -z to +z across the membrane. So I used pull-geometry=direction in gromacs 5.0.4 (as per gromacs site= http://www.gromacs.org/Documentation/How-tos/Potential_of_Mean_Force), as I cannot use pull-geimetry=distance. Every thing completed correctly (seems to me), but when I used gmx wham on the pullf.xvg files, PMF profile was on the positive side. PMF increased from 0 (bulk water) to 60 at the center of the membrane and than again decreased to the 0 (bulk water on the other side). I all the literature, PMF values for the molecule crossing a membrane is on the negative side and minimum at the center. I am confused about the result. Did I do something wrong with the parameters or understanding the PMF curve wrongly. can any one give their suggestion on this. thanks in advance of user time and help. with regards Mahender Singh -- 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] umbrella sampling and PMF calculation by using pull-geometry=direction in gromacs 5.0.4
Thanks Chris for your help I am using Isoniazid drug and the membrane model is a mixture of different lipid types (POPE,POPC,POPI,POPS,cholesterol) in a ratio mimicking the plasma membrane more closely as compared to the simple single lipid type membrane model. I have attached the PMF plot (attachment, shared link), and sorry for the partial PMF graph as one can see sampling is not sufficient , as I stopped further umbrella sampling, because of strange results. One is made by using pull-geometry=distance, free, energy on the negative side (limited to the one leaflet, as distance between two group become zero drug will not move onto the other side) and other by using pull-geometry=direction for the same drug i.e. isoniazid, free energy on the positive side. https://onedrive.live.com/redir?resid=DA38458F80BE68E9!192authkey=!ACGecvNH6tPzIloithint=folder%2c All the parameters were same except pull-geomerty i.e distance or direction. But free energy graph is completely opposite in both the cases and this should not be , as I thinks. As for the same drug free energy profile should not be completely opposite for the one drug, so may be I making some mistake in the umbrella sampling parameters. Can you provide me some suggestion on this topic. Thanks in advance for help. with regards Mahender Singh Hello good morning to all I did steered md simulation by using following code ;pull code pull= umbrella pull_geometry= direction pull_dim= N N Y pull_coord1_vec=0 0 1 pull_start= yes pull_ngroups=2 pull-ncoords=1 pull_coord1_groups= 1 2 pull_group1_name= NPROT_ref pull_group2_name= LIG pull_coord1_rate= 0.004; 0.004 nm per ps = 4 nm per ns pull_coord1_k= 1000; kJ mol^-1 nm^-2 pull_nstxout= 500; every 1 ps pull_nstfout= 500; every 1 ps And then used these results of SMD for umbrella sampling (total umbrella window =30 across the membrane) by using following code pull= umbrella pull_geometry= direction pull_dim= N N Y pull_coord1_vec=0 0 1 pull_start= yes pull_ngroups=2 pull-ncoords=1 pull_coord1_groups= 1 2 pull_group1_name= NPROT_ref pull_group2_name= LIG pull_coord1_rate= 0.0 pull_coord1_k= 1000; kJ mol^-1 nm^-2 pull_nstxout= 500; every 1 ps pull_nstfout= 500; every 1 ps In my case, I am moving a molecule from -z to +z across the membrane. So I used pull-geometry=direction in gromacs 5.0.4 (as per gromacs site= http://www.gromacs.org/Documentation/How-tos/Potential_of_Mean_Force), as I cannot use pull-geimetry=distance. Every thing completed correctly (seems to me), but when I used gmx wham on the pullf.xvg files, PMF profile was on the positive side. PMF increased from 0 (bulk water) to 60 at the center of the membrane and than again decreased to the 0 (bulk water on the other side). I all the literature, PMF values for the molecule crossing a membrane is on the negative side and minimum at the center. I am confused about the result. Did I do something wrong with the parameters or understanding the PMF curve wrongly. can any one give their suggestion on this. thanks in advance of user time and help. with regards Mahender Singh -- 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. -- Message: 3 Date: Sun, 3 May 2015 12:25:01 + From: Christopher Neale chris.ne...@alum.utoronto.ca To: gmx-us...@gromacs.org gmx-us...@gromacs.org Subject: Re: [gmx-users] umbrella sampling and PMF calculation by using pull-geometry=direction in gromacs 5.0.4 Message-ID: 1430655898617.32...@alum.utoronto.ca Content-Type: text/plain; charset=iso-8859-1 Better yet, repeat something that is already out there in the literature. PMFs for water, lipids, and some amino acid side chains across the bilayer have been tested extensively. Chris. From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se gromacs.org_gmx-users-boun...@maillist.sys.kth.se on behalf of mahender singh pharmbioc...@live.com Sent: 03 May 2015 01:07 To: gromacs user_list Subject: [gmx-users] umbrella sampling and PMF calculation by using pull-geometry=direction in gromacs 5.0.4 Hello good morning to all I did steered md simulation by using following code ;pull code pull= umbrella pull_geometry= direction pull_dim= N N Y pull_coord1_vec=0 0 1 pull_start= yes pull_ngroups=2 pull-ncoords=1
Re: [gmx-users] umbrella sampling and PMF calculation by using pull-geometry=direction in gromacs 5.0.4
Take a look at profiles in the literature for arginine across a bilayer. It has a maximum at the center. Probably true for any molecule with a large charge/molecular weight ratio. For more help you'd likely have to reveal your system and provide an image of the PMF. However, there is no reason to think that you've got a problem unless you're working with a small hydrophobic molecule (in which case the dG should almost certainly be the inverse of what you see). One test you can do is to compare the free energy of solvation of your molecule in water and octane using the double-decoupling method. Chris. From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se gromacs.org_gmx-users-boun...@maillist.sys.kth.se on behalf of mahender singh pharmbioc...@live.com Sent: 03 May 2015 01:07 To: gromacs user_list Subject: [gmx-users] umbrella sampling and PMF calculation by using pull-geometry=direction in gromacs 5.0.4 Hello good morning to all I did steered md simulation by using following code ;pull code pull= umbrella pull_geometry= direction pull_dim= N N Y pull_coord1_vec=0 0 1 pull_start= yes pull_ngroups=2 pull-ncoords=1 pull_coord1_groups= 1 2 pull_group1_name= NPROT_ref pull_group2_name= LIG pull_coord1_rate= 0.004; 0.004 nm per ps = 4 nm per ns pull_coord1_k= 1000; kJ mol^-1 nm^-2 pull_nstxout= 500; every 1 ps pull_nstfout= 500; every 1 ps And then used these results of SMD for umbrella sampling (total umbrella window =30 across the membrane) by using following code pull= umbrella pull_geometry= direction pull_dim= N N Y pull_coord1_vec=0 0 1 pull_start= yes pull_ngroups=2 pull-ncoords=1 pull_coord1_groups= 1 2 pull_group1_name= NPROT_ref pull_group2_name= LIG pull_coord1_rate= 0.0 pull_coord1_k= 1000; kJ mol^-1 nm^-2 pull_nstxout= 500; every 1 ps pull_nstfout= 500; every 1 ps In my case, I am moving a molecule from -z to +z across the membrane. So I used pull-geometry=direction in gromacs 5.0.4 (as per gromacs site= http://www.gromacs.org/Documentation/How-tos/Potential_of_Mean_Force), as I cannot use pull-geimetry=distance. Every thing completed correctly (seems to me), but when I used gmx wham on the pullf.xvg files, PMF profile was on the positive side. PMF increased from 0 (bulk water) to 60 at the center of the membrane and than again decreased to the 0 (bulk water on the other side). I all the literature, PMF values for the molecule crossing a membrane is on the negative side and minimum at the center. I am confused about the result. Did I do something wrong with the parameters or understanding the PMF curve wrongly. can any one give their suggestion on this. thanks in advance of user time and help. with regards Mahender Singh -- 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.
