Predicting biomolecular binding kinetics: A review

J Wang, HN Do, K Koirala, Y Miao - Journal of Chemical Theory …, 2023 - ACS Publications
Journal of Chemical Theory and Computation, 2023ACS Publications
Biomolecular binding kinetics including the association (k on) and dissociation (k off) rates
are critical parameters for therapeutic design of small-molecule drugs, peptides, and
antibodies. Notably, the drug molecule residence time or dissociation rate has been shown
to correlate with their efficacies better than binding affinities. A wide range of modeling
approaches including quantitative structure-kinetic relationship models, Molecular Dynamics
simulations, enhanced sampling, and Machine Learning has been developed to explore …
Biomolecular binding kinetics including the association (kon) and dissociation (koff) rates are critical parameters for therapeutic design of small-molecule drugs, peptides, and antibodies. Notably, the drug molecule residence time or dissociation rate has been shown to correlate with their efficacies better than binding affinities. A wide range of modeling approaches including quantitative structure-kinetic relationship models, Molecular Dynamics simulations, enhanced sampling, and Machine Learning has been developed to explore biomolecular binding and dissociation mechanisms and predict binding kinetic rates. Here, we review recent advances in computational modeling of biomolecular binding kinetics, with an outlook for future improvements.
ACS Publications
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