Intra-protein hydrogen bonding is dynamically stabilized by electronic polarization

Abstract

Molecular dynamics (MD) simulation has been carried out to study dynamical stability of intra-protein hydrogen bonds based on two set of atomic charges, the standard AMBER charge and the polarized protein-specific charge (PPC). The latter is derived from quantum mechanical calculation for protein in solution using a recently developed molecular fractionation with conjugate caps-Poisson-Boltzmann (MFCC-PB) approach and therefore includes electronic polarization effect of the protein at native structure. MD simulations are performed for a number of benchmark proteins containing helix and/or beta sheet secondary structures. The computational result shows that occupancy percentage of hydrogen bonds averaged over simulation time, as well as the number of hydrogen bonds as a function of simulation time, is consistently higher under PPC than AMBER charge. In particular, some intra-protein hydrogen bonds are found broken during MD simulation using AMBER charge but they are stable using PPC. The breaking of some intra-protein hydrogen bonds in AMBER simulation is responsible for deformation or denaturing of some local structures of proteins during MD simulation. The current study provides strong evidence that hydrogen bonding is dynamically more stable using PPC than AMBER charge, highlighting the stabilizing effect of electronic polarization on protein structure.