Absolute Binding Free Energies Between T4 Lysozyme and 115 Small Molecules: Calculations Based on Multiple Rigid Receptor Structures

Free energy calculations can predict noncovalent binding affinities, which play an important role in drug design. However, there are many challenges to performing accurate calculations, such as insufficient configurational sampling and solvation effects. There are mainly two strategies to perform free energy predictions: fast but inaccurate molecular docking methods, and accurate but slow molecular dynamics simulations along an alchemical pathway. Xie's research group has developed a program, AlGDock, which is based on its recently derived implicit ligand theory. This approach combines advantages of both methods: It can get the free energy results more accurately than docking and spend less time than alchemical simulations. In this talk, Xie will describe its application to a protein-ligand system, T4 lysozyme and 115 small molecules and discuss how the implicit solvent models, such as the Generalized Born and Poisson-Boltzmann model, influence free energy predictions.