@article {Tang155275, author = {Zhiye Tang and Chia-en A. Chang}, title = {Binding Thermodynamics and Kinetics Calculations Using Chemical Host and Guest: A Comprehensive Picture of Molecular Recognition}, elocation-id = {155275}, year = {2017}, doi = {10.1101/155275}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Understanding the fine balance between changes of entropy and enthalpy and the competition between a guest and water molecules in molecular binding is crucial in fundamental studies and practical applications. Experiments provide measurements. However, illustrating the binding/unbinding processes gives a complete picture of molecular recognition not directly available from experiments, and computational methods bridge the gaps. Here, we investigated guest association/dissociation with β-cyclodextrin (β-CD) by using microsecond-timescale molecular dynamics (MD) simulations, post-analysis and numerical calculations. We computed association and dissociation rate constants, enthalpy, and solvent and solute entropy of binding. All the computed values of kon, koff, ΔH, ΔS, and ΔG could be compared with experimental data directly and agreed well with experiment findings. Water molecules play a crucial role in guest binding to β-CD. Collective water/β-CD motions could contribute to different computed kon and ΔH values by using GAFF-CD and q4MD-CD force fields for β-CD, mainly because of the motion of β-CD that provides different hydrogen-bond networks of water molecules in the cavity of free β-CD and the strength of desolvation penalty. Both force fields resulted in similar computed ΔG from independently computed kinetics rates and thermodynamics properties (ΔH, ΔS), enthalpy-entropy compensation and the same driving forces of binding, non-polar attractions between solutes and entropy gain of desolvating water molecules. However, the balances of ΔH and -TΔS are not identical. The study further interprets experiments, deepens our understanding of ligand binding, and suggests strategies for force field parameterization.}, URL = {https://www.biorxiv.org/content/early/2017/06/25/155275}, eprint = {https://www.biorxiv.org/content/early/2017/06/25/155275.full.pdf}, journal = {bioRxiv} }