Reconciling NMR Structures of the HIV-1 Nucleocapsid Protein NCp7 Using Extensive Polarizable Force Field Free-Energy Simulations.
Léa El KhouryFrédéric CélerseLouis LagardèreLuc-Henri JollyEtienne DeratZeina HobaikaRichard G MarounPengyu RenSerge BouazizNohad GreshJean-Philip PiquemalPublished in: Journal of chemical theory and computation (2020)
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.
Keyphrases
- antiretroviral therapy
- high resolution
- hiv positive
- hiv infected
- magnetic resonance
- human immunodeficiency virus
- hepatitis c virus
- hiv testing
- amino acid
- protein protein
- solid state
- single molecule
- binding protein
- men who have sex with men
- molecular dynamics simulations
- respiratory syndrome coronavirus
- coronavirus disease