Accelerating Conformational Sampling in Free Energy Calculations

摘要: Molecular dynamics are increasingly used to construct conformational ensembles of biochemical systems. The accuracy these is determined by the underlying model and extent sampling during simulation. Biochemical systems can have motion on time scales that vary several orders magnitude, must all be described before a specific validated. For this reason research into enhanced methods accelerate vital progress molecular dynamics. This dissertation describes validation application replica exchange accelerated (REXAMD) method in context free energy calculations. In chapters 2 3 REXAMD validated using simple convergence shown an improvement over classical Additionally, various improve statistical behavior investigated. chapter 4 gradient-augmented Harmonic Fourier Beads, minimum pathway method, study change ion selectivity peptide from KcsA potassium channel. robustness models, ranging quantum mechanical, investigated importance observed. Finally 5, I propose modification AMBER package which allows calculation absolute binding energies computed