Investigation of domain structure in proteins via molecular dynamics simulation: application to HIV-1 protease dimer

A general method for the investigation of domain structure in proteins based on the analysis of molecular dynamics simulations is described. The method is based on the idea that residues of a domain move in concert with one another, as determined by the analysis of the cross-correlation coefficients for atomic displacements computed from the simulation history. The correlation coefficients are displayed in the form of a two-dimensional "dynamical cross-correlation map" (DCCM) on which each type of protein domain has a signature appearance. Domain-domain correlations appear as off-diagonal elements in the DCCM and indicate novel aspects of action-at-a-distance and through-space communication in the structure which originate uniquely in the dynamical motions. The method is illustrated here with an analysis of a molecular dynamics simulation on HIV-1 protease (HIV-1 PR), a protein dimer that exhibits a diversity of secondary structural motifs.