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

preprint
revised on 27.02.2020 and posted on 28.02.2020 by Léa El Khoury, Frédéric Célerse, Louis Lagardere, Luc-Henri Jolly, Étienne Derat, Zeina Hobaika, Richard G. Maroun, Pengyu Ren, Serge Bouaziz, Nohad Gresh, Jean-Philip Piquemal
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.

Funding

Extreme-scale Mathematically-based Computational Chemistry

European Research Council

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Specificity and Selectivity in Protein-Ion Binding

National Institute of General Medical Sciences

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History

Email Address of Submitting Author

jean-philip.piquemal@sorbonne-universite.fr

Institution

Sorbonne Université

Country

France

ORCID For Submitting Author

0000-0001-6615-9426

Declaration of Conflict of Interest

no conflict of interest

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