Probing the mechanism of pH-induced large-scale conformational changes in dengue virus envelope protein using atomistic simulations.

ABSTRACT: One of the key steps in the infection of the cell by dengue virus is a pH-induced conformational change of the viral envelope proteins. These envelope proteins undergo a rearrangement from a dimer to a trimer, with large conformational changes in the monomeric unit. In this article, metadynamics simulations were used to enable us to understand the mechanism of these large-scale changes in the monomer. By using all-atom, explicit solvent simulations of the monomers, the stability of the protein structure is studied under low and high pH conditions. Free energy profiles obtained along appropriate collective coordinates demonstrate that pH affects the domain interface in both the conformations of E monomer, stabilizing one and destabilizing the other. These simulations suggest a mechanism wit

SUBMITTER: Prakash MK 

PROVIDER: S-EPMC2905125 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature