Biological and Medicinal Chemistry

Reconciling NMR Structures of the HIV-1 Nucleocapsid Protein (NCp7) using Extensive Polarizable Force Field Free-Energy Simulations

Abstract

Using polarizable (AMOEBA) and non-polarizable (CHARMM) force fields, we compare the relative free-energy stability of two extreme conformations of the HIV-1 NCp7 nucleocapsid that had been previously experimentally advocated to prevail in solution. Using accelerated sampling techniques, we show that they differ in stability by no more than 0.75-1.9 kcal/mol depending on the reference protein sequence. While the extended form appears to be the most probable structure, both forms should thus coexist in water explaining the differing NMR findings.

Content

Thumbnail image of NCP7__JCTC.pdf

Supplementary material

Thumbnail image of NCP7_SI.pdf
NCP7 SI