Hi, I am trying to perform an alchemical free energy perturbation with gromacs, since I am approaching this technique for the first time. So, it would be so nice if you could help me to clarify some doubt.
I have built my system, which is composed of 1 protein, 2 cofactors, and 1 ligand that should changes from state A to B. I used FESetup to make the topology for my ligand. The change I want to apply to my molecule is just the transformation of a hydrogen into chlorine, so I do not have dummy atoms involved. This is the only string that changes from state A to B in my ligand topology: [Atoms] ; Nr type resnm atom cgnr charge mass typeB chargeB massB 30 h4 1 LIG H30 30 0.158051 1.0080 cl -0.078297 35.4500 So, I have the complex.gro and complex.top, I made some minimization tests and everything seems good. I have some doubts on the procedure I'm supposed to follow to perform FEP calculation. Some questions: 1) Can I perform the calculation in a single step with soft core potential enabled? I mean, is it correct to transform directly the hydrogen into a chlorine instead of using 2 topologys and 2 complexes, where in the first step I transform the hydrogen into dummy atom, and in the second I transform the dummy atom into chlorine. Using soft core potential I can perform any kind of transformation in single step, or are there some cases where I need to use different procedures? 2) Referring to BevanLab Tutorial 6: Free Energy Calculation ( http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gm x-tutorials/free_energy/index.html), I have to perform every step of molecular dynamics at every Lambda value, is that right? 3) I run a test minimization step (mdp file attached) of my complex at the last "init-lambda-state", 15 in my case. Looking at the .trr output file I can see that the bond between the carbon and the hydrogen which should be trasformed is longer than a normal C-H bond, but the atom is still recognized as hydrogen (picture "http://tinypic.com/r/2wp11dh/9": purple -> init-lambda-state = 0 ; blue -> init-lambda-state = 15). I was wondering if this is what I am supposed to see, so if gromacs is considering the state B of my system where I have chlorine bound to carbon instead hydrogen. I am apologize if my questions are technically incorrect. As I said it is the first time I'm approaching to free energy perturbation and every kind of help and suggestion is really appreciated. Thank you very much in advance. Best regards, Davide Bonanni ---------------------------------------------------------- Davide Bonanni, PhD student Dept. Science and Drug Technology University of Turin (UniTO) - Italy Mobile +39 3409726272 <+39%20340%20972%206272> ----------------------------------------------------------
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