Enhanced Conformational Sampling of Carbohydrates using Biasing Potential and Solute Tempering Replica Exchange: Application to the N-glycan on the HIV gp120 Envelope Protein

Abstract

Conformational sampling of complex molecular systems is always a challenge in computer simulations. To tackle this problem, a range of enhanced sampling methods have been developed. However, each method typically only shows distinct advantages in specific systems. Therefore, new approaches aim to combine the complementarity of different enhanced sampling algorithms to achieve a better performance. In this study, we propose a new algorithm to combine the advantages of two Hamiltonian replica exchange methods designed to improve sampling of specific degrees of freedom using biasing potentials and of global conformational properties, including solute-solvent interactions via solute tempering.1-2 The new method produces improved sampling for polysaccharides with coupled linkages, including branch points. The method is applied to N-glycans found on the HIV gp120 envelope protein that show potential application in the design of HIV vaccines.