Residue Energy and Mobility in Sequence to Global Structure and Dynamics of a HIV-1 protease (1DIFA) By A Coarse-Grained Monte Carlo Simulation

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Physics and Astronomy


Energy, mobility, and structural profiles of residues in a specific sequence of human immunodeficiency virus (HIV)-1 protease chain and its global conformation and dynamics are studied by a coarse-grained computer simulation model on a cubic lattice. HIV-1 protease is described by a chain of 99 residues (nodes) in a specific sequence (1DIFA) with N- and C-terminals on the lattice, where empty lattice sites represent an effective solvent medium. Internal structures of the residues are ignored but their specificities are captured via an interaction (epsilon(ij)) matrix (residue-residue, residue-solvent) of the coefficient (f epsilon(ij)) of the Lennard-Jones potential. Simulations are performed for a range of interaction strength (f) with the solvent-residue interaction describing the quality of the solvent. Snapshots of the protein show considerable changes in the conformation of the protein on varying the interaction. From the mobility and energy profiles of the residues, it is possible to identify the active (and not so active) segments of the protein and consequently their role in proteolysis. Contrary to interaction thermodynamics, the hydrophobic residues possess higher configurational energy and lower mobility while the electrostatic and polar residues are more mobile despite their lower interaction energy. Segments of hydrophobic core residues, crucial for the structural evolution of the protein are identified-some of which are consistent with recent molecular dynamics simulation in context to possible clinical observations. Global energy and radius of gyration of the protein exhibit nonmonotonic dependence on the interaction strength (f) with opposite trends, e.g., rapid transition into globular structure with higher energy. Variations of the rms displacement of the protein and that of a tracer residue, Gly(49), with the time steps show how they slow down on increasing the interaction strength.

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Journal of Chemical Physics