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

28 February 2020, Version 3
This content is a preprint and has not undergone peer review at the time of posting.


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.


HIV-1 infection
Molecular Dynamics Simulation Study
AMOEBA polarizable
Polarizable force fields
Free energy calculations
Steered Molecular Dynamics Simulation
Umbrella Sampling SimulationsFree energy prediction

Supplementary materials

NCP7 SI-rev


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