MD simulation of coxsackievirus capsid : motion of integurin-binding

Abstract

Coxsackievirus A9, a human pathogen causing symptoms ranging from common colds to fatal infections of the central nervous system, is an icosahedral single-strand RNA virus that belongs to the genus Enterovirus of the family Picornaviridae. Molecular dynamics simulation was performed for the complex of the coxsackievirus A9 capsid and two molecules of antiviral drug, WIN51171, under rotational symmetry boundary conditions, using the APRICOT program. For the simulation, the protonation states of histidine residues in the X-ray structure (pdb-id:1D4M) were determined by considering the local structure around the residues and by calculation with the Protonate3D program of the modeling software MOE. Because the integrin binding site, i.e. the C-term of VP1 of the capsid, is disordered in the X-ray analysis, the initial structure of the site was taken from the X-ray structure of foot-and-mouth disease capsid. Electrostatic potential around WIN51171 and myristic acid that is bound to the N-term of VP4 was calculated with HF/6-31G* level. The two-conformational two-stage RESP fit was used to determine their atomic charges. The integrin binding site showed large fluctuation in the water zone over the outer surface of the capcid.