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

Overview

Journal J Chem Theory Comput

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2020 Mar 18

PMID 32178519

Citations 4

Authors

Lea El Khoury

Frederic Celerse

Louis Lagardere

Luc-Henri Jolly

Etienne Derat

Zeina Hobaika

Richard G Maroun

Pengyu Ren

Serge Bouaziz

Nohad Gresh

Jean-Philip Piquemal

Affiliations

Soon will be listed here.

Abstract

Using polarizable (AMOEBA) and nonpolarizable (CHARMM) force fields, we compare the relative free energy stability of two extreme conformations of the HIV-1 nucleocapsid protein NCp7 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.

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