The development of replica-exchange-based free-energy methods

摘要: The calculation of relative free energies that involve large reorganizations the environment is one great challenges condensed-phase simulation. Such calculations are particular importance in protein−ligand free-energy calculations. To meet this challenge, we have developed new techniques combine advantages replica-exchange method with perturbation (FEP) and finite-difference thermodynamic integration (FDTI). These tested compared FEP, FDTI, adaptive umbrella weighted histogram analysis (AdUmWHAM) on challenging hydration energy methane water. This involves a solvent configurational change. Through use moves along λ-coordinate, configurations sampled λ allowed to mix, which leads dramatic improvements sampling, an efficient reduction random sampling error, o...