[gmx-users] Umbrella sampling with restraint on the center of mass of ligand
Dear GMX users I am doing umbrella sampling to obtain a PMF relative to the translocation of a ligand within a membrane protein. I want to add an harmonic potential to restrain the center of mass of the ligand in each window , similarly to the protocols used by Subramanian et al ( https://pubs.acs.org/doi/pdf/10.1021/acs.jcim.8b00624 ; https://www.sciencedirect.com/science/article/pii/S0005273615004319?via%3Dihub ) Yet, I am not certain of which .mdp settings I should use to accomplish my goal, the documentation is not clear and most infomation I find refers to the application of harmonic potentials when the reaction coordinate is a distance between two groups. Here are my .mdp settings: pull= yes pull_print_com = yes pull_print_ref_value= yes pull_nstxout= 500 pull_nstfout= 0 pull_ncoords= 1 ; only one reaction coordinate pull_ngroups= 1 pull_coord1_geometry= direction-periodic pull_coord1_vec = 0 0 1 pull-coord1-origin = 0 0 0 pull_group1_name= LIG pull_coord1_groups = 0 1 pull_coord1_type= umbrella ; harmonic potential pull_coord1_start = yes ; define initial COM distance > 0 pull_coord1_rate= 0.0 ; restrain in place pull_coord1_k = 500 ; kJ mol^-1 nm^-2 Essentially, I created a vector between the center-of-mass of the ligand and an absolute reference (0,0,0) and I had to use pull_coord1_geometry = direction-periodic ( instead of direction) ,because the simulation crashed. This also forces me to perform an NVE simulation. Is this the right way of applying a an harmonic restraint on the center-of-mass of a ligand for umbrella sampling? Are these settings correct? Any help is appreaciated. Thanks in advance -- 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] Comparison of PMF profiles in different states of a protein
Hi I am studying the movement of a molecule in two different states of a protein. To do so, I want to calculate a PMF profile in each state using umbrella sampling. My reaction coordinate is the distance between the center-of-mass of a fixed residue and the center-of-mass of the molecule. My goal is to compare both profiles. Although I am using an internal coordinate of the system, I need to make the profiles comparable and to eliminate fluctuations of the reference residue (which is already in a rigid zone of the protein). To that end, I am thinking to adopt a similar procedure to the one used by Hub et al ( https://pubs.acs.org/doi/abs/10.1021/ja102133x), in which I plan to align the trajectories of all windows to a global average structure and I calculate the difference between the coordinates of the reference residue on the trajectory and of the average structure. Only after, I calculate the free energy with the modified CV. Can anyone give me an opinion whether this procedure makes any sense? Furthermore, how can I ensure that both profiles have the same energy zero? If I use WHAM to calculate the profiles, even if I supply initial conformations with the same CV value to both states (because g_wham zeroes the profiles at the first supplied conformation), due to WHAM reweigthing the weights of the conformations in each state will be different? Am I correct? In that case would it be better to use umbrella integration? Any help is appreciated. Thanks in advance. -- 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.
