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

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.

SUBMITTER: El Khoury L

PROVIDER: S-EPMC7375347 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

El Khoury Léa L Célerse Frédéric F Lagardère Louis L Jolly Luc-Henri LH Derat Etienne E Hobaika Zeina Z Maroun Richard G RG Ren Pengyu P Bouaziz Serge S Gresh Nohad N Piquemal Jean-Philip JP

Journal of chemical theory and computation 20200330 4

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 th ...[more]

PMID: 32178519

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