Hi,
I am familiar with performing MD simulations using Gromacs on protein-ligand complexes. However, BAR is a new technique to me and I need specific clarification of the decoupling sequence followed.
Firstly, if A represents the initial state and B represents the end state, do I carry out two series of simulations in Gromacs (i.e. at different values of lambda) for:
1. VdW interactions decoupling (where couple-lambda0 = vdw and couple-lambda1 = none)
2. Coulombic interactions decoupling (where couple-lambda0 = vdwq and couple-lambda1 = vdw)
Secondly, must I perform these two transformations for both the solvated ligand-protein complex and the solvated ligand separately?
Thirdly, how do I combine these results to produce a meaningful Gibbs free energy of binding for my complex?
As with the free energy perturbation approach: (1) VdW and Coulombic interactions can be decoupled simultaneously or stepwise; if stepwise, first the Coulombic interactions. (2) The two transformations must be performed separately for both the solvated ligand-protein complex and the solvated ligand.
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