生物大分子的计算机模拟.PDFVIP

生物大分子的计算机模拟 3.1 自由能计算 (Free Energy Calculations) 主讲：张志勇（Zhiyong Zhang ） zzyzhang@ 电话 课件下载地址： /~zzyzhang 1 Outline • Importance of free energy calculations （重要性） • Difficulty of calculating free energy by computer simulations （困难） • Methods and applications （方法介绍） 2 Free Energy is Important Free energy is one of the most important thermodynamic quantities (reaction equilibrium, solvation, stability, and kinetics, etc) • Protein-protein and protein-ligand interactions (binding constants, association and dis-association) • Mutation analysis • Rational drug design • Protein folding/unfolding 3 4 5 6 7 Thermodynamic Properties • Mechanical properties: related to the derivative of the partition function Q Internal energy, pressure, and heat capacity, etc. • Thermal properties: related to the partition function Q itself Free energy, chemical potential, and entropy, etc. Partition function for the canonical ensemble: 8 Difficulty of Calculating Free Energy Internal energy U: High energy states have a very low probability and make an insignificant contribution to the integral, so we can generate accurate estimate of U by MD or MC. Helmholtz f