Thermodynamic properties of solvated peptides from selective integrated tempering sampling with a new weighting factor estimation algorithm

Conformational sampling under rugged energy landscape is always a challenge in computer simulations. The recently developed integrated tempering sampling, together with its selective variant (SITS), emerges to be a powerful tool in exploring the free energy landscape or functional motions of various systems. The estimation of weighting factors constitutes a critical step in these methods and requires accurate calculation of partition function ratio between different thermodynamic states. In this work, we propose a new adaptive update algorithm to compute the weighting factors based on the weighted histogram analysis method (WHAM). The adaptive-WHAM algorithm with SITS is then applied to study the thermodynamic properties of several representative peptide systems solvated in an explicit water box. The performance of the new algorithm is validated in simulations of these solvated peptide systems. We anticipate more applications of this coupled optimisation and production algorithm to other complicated systems such as the biochemical reactions in solution.