Title

Monte Carlo Simulations Of Hiv Capsid Protein Homodimer

Abstract

Capsid protein (CA) is the building block of virus coats. To help understand how the HIV CA proteins self-organize into large assemblies of various shapes, we aim to computationally evaluate the binding affinity and interfaces in a CA homodimer. We model the N- and C-terminal domains (NTD and CTD) of the CA as rigid bodies and treat the five-residue loop between the two domains as a flexible linker. We adopt a transferrable residue-level coarse-grained energy function to describe the interactions between the protein domains. In seven extensive Monte Carlo simulations with different volumes, a large number of binding/unbinding transitions between the two CA proteins are observed, thus allowing a reliable estimation of the equilibrium probabilities for the dimeric vs monomeric forms. The obtained dissociation constant for the CA homodimer from our simulations, 20-25 μM, is in reasonable agreement with experimental measurement. A wide range of binding interfaces, primarily between the NTDs, are identified in the simulations. Although some observed bound structures here closely resemble the major binding interfaces in the capsid assembly, they are statistically insignificant in our simulation trajectories. Our results suggest that although the general purpose energy functions adopted here could reasonably reproduce the overall binding affinity for the CA homodimer, further adjustment would be needed to accurately represent the relative strength of individual binding interfaces. (Figure Presented).

Publication Date

7-27-2015

Publication Title

Journal of Chemical Information and Modeling

Volume

55

Issue

7

Number of Pages

1361-1368

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1021/acs.jcim.5b00126

Socpus ID

84938089999 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84938089999

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