Dear All, I am modeling the binding free energy between a molecule of sodium cholate and a 2D nanosheet by using steered MD and umbrella sampling as guided by Gromacs Tutorial 3 ( http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/index.html ).
The small molecule has a strong binding with the surface of nanosheet. I first performed a Steered MD to pull the molecule away from the surface. The loading rate is low as 0.01 nm/ns, the force constant for pulling is 1000 kJ/nm2 and the output frequency of configuration is 1 frame very 100 ps. However, due to the strong binding, the COM distance between the molecule and nanosheet has a big jump (~0.4 nm) at the detachment. I cannot extract successive sufficiently configurations at the moment of detachment for umbrella sampling (10 ns sampling). Even if I choose every configurations near the detachment for sampling, the histograms still have a wide gap and the curve in the energy profile is noncontinuous. I have tried to increase the force constant for pulling and even decreased the loading rate. But the problem still exists. I wonder if you have any experience to solve this problem. It would be appreciated if you could provide any suggestion. Should I use the other method for free energy calculation as in the Gromacs Tutorial 6 ( http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/free_energy/index.htm), instead of using SMD and umbrella sampling? But there are also some questions when I use this method. First, the molecule is negatively charged. When I uncouple the electrostatic interactions, should I uncouple the sodium ions? If so, I am calculating the free energy of the molecule and its neutralizing ion, not only the molecule. Is it correct? If I am only interested in the molecule, what should I do? In this method, unlike the umbrella sampling, we only can get the free energy change, not the energy curve that includes the information of energy barrier. Is it correct? Many thanks for your helps in advance! Best, Wenpeng Zhu -- 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.
