Journal of chemical information and modeling 2017 04 20() doi 10.1021/acs.jcim.7b00011
HIV-1 capsid proteins (CAs) assemble into a capsid that encloses the viral RNA. The binding between a pair of C-terminal domains (CTDs) constitutes a major interface in both the CA dimers and the large CA assemblies. Here we attempt to use a general residue-level coarse-grained model to describe the interaction between two isolated CTDs in Monte Carlo simulations. With the standard parameters that depend only on the residue types, the model predicts a much weaker binding in comparison to the experiments. Detailed analysis reveals that some Lennard-Jones parameters are not compatible with the experimental CTD dimer structure, thus resulting in an unfavorable interaction energy. To improve the model for the CTD binding, we introduce ad hoc modifications to a small number of Lennard-Jones parameters for some specific pairs of residues at the binding interface. Through a series of extensive Monte Carlo simulations, we identify the optimal parameters for the CTD-CTD interactions. With the refined model parameters, both the binding affinity (with a dissociation constant of 13 ± 2 μM) and the binding mode are in good agreement with the experimental data. This study demonstrates that the general interaction model based on the Lennard-Jones potential, with some modest adjustment of the parameters for key residues, could correctly reproduce the reversible protein binding, thus potentially applicable for simulating the thermodynamics of the CA assemblies.