Title: Modeling Ligand-receptor Binding Kinetics and Thermodynamics: A Comprehensive Picture of Molecular Recognition
Time: 11:00 a.m.
Location: Room 202 MRB
Presenter: Professor Chia-en A. Chang (Department of Chemistry, University of California, Riverside, California)
Non-covalent molecular recognition plays a crucial role in biology, chemistry medicine, and material sciences. Kinetic binding rate constants, together with equilibrium constants, provide a complete view of molecular recognition. In addition, modeling ligand-receptor binding/unbinding pathways can provide insights into molecular association, including intermolecular interactions, changes of solvent and solute entropy, barriers to binding, and conformational changes in the intermediate states. This presentation discusses the complete binding enthalpy and entropy profiles of both solute and solvent. We applied molecular dynamics (MD) simulations for multiple guests binding to beta-cyclodextrin to compute binding enthalpy, entropy, and rate constants. I will also talk about post-analyzing the trajectories for solvent and solute entropy calculations, conformational changes during binding and the importance in solvent effects. The sensitivity of use of different force fields to model conformational flexibility and to compute thermodynamic and kinetic values will be discussed as well. In addition, different methods for computing binding/unbinding free energy profile, such as the umbrella sampling method and milestoning theory, will be discussed during the talk.