Ab initio molecular metadynamics simulation for S-nitrosylation by nitric oxide: S-nitroxide as the key intermediate

Abstract

Snitric oxide plays important roles in protein S-nitrosylation, in which thionitroxide (RSNHO) may serve as a signal at the cysteine site. Car-Parrinello metadynamics method was employed to investigate the possible fate of thionitroxide (S-nitroxide) in S-nitrosylation, focusing on S–N decomposition that leads to HNO, NO and even thiyl radical. As a result, the lowest-energy pathway from thiol towards S-nitrosothiol via thionitroxide was predicted to be feasible in a form of RSH + 2 NO• = RSNO + HNO. This equilibrium for the chemical modification was likely controlled by surrounding environment, that is, by aqueous solution and methanol in this simulation, and probably by dynamic structure of polar residues in S-nitrosylated protein. This work implied that the general importance of the temporal and spatial transformation of allosteric effect in a predictive modelling of protein post-translational modification could be briefly attested with the artificially intelligent CPMD algorithm.