ModBind, a Rapid Simulation-Based Predictor of Ligand Binding and Off-Rates DOI Creative Commons

William Sinko,

Blake Mertz, Takafumi Shimizu

и другие.

Journal of Chemical Information and Modeling, Год журнала: 2024, Номер 65(1), С. 265 - 274

Опубликована: Дек. 16, 2024

In rational drug discovery, both free energy of binding and the half-life (koff) are important factors in determining efficacy drugs. Numerous computational methods have been developed to predict these properties, many which rely on molecular dynamics (MD) simulations. While free-energy (thermodynamic equilibrium predictions) well validated demonstrated ability drive daily synthesis decisions a commercial discovery setting, prediction koff (kinetics has had limited validation, predictive largely not deployed settings. We ModBind, novel method for MD simulation-based predictions. ModBind similar accuracy current state-of-the-art methods. Additionally, performs ∼100 times faster than most available or methods, allowing widespread use by modeling community. relative changes primarily useful optimization congeneric series, our requires no structural similarity between ligands, making an absolute predictor koff. is thus tool that can be used virtual screening diverse it distinct from also discuss conditions enable approximate ligand using limitations this approach.

Язык: Английский

ModBind, a Rapid Simulation-Based Predictor of Ligand Binding and Off-Rates DOI Creative Commons

William Sinko,

Blake Mertz, Takafumi Shimizu

и другие.

Journal of Chemical Information and Modeling, Год журнала: 2024, Номер 65(1), С. 265 - 274

Опубликована: Дек. 16, 2024

In rational drug discovery, both free energy of binding and the half-life (koff) are important factors in determining efficacy drugs. Numerous computational methods have been developed to predict these properties, many which rely on molecular dynamics (MD) simulations. While free-energy (thermodynamic equilibrium predictions) well validated demonstrated ability drive daily synthesis decisions a commercial discovery setting, prediction koff (kinetics has had limited validation, predictive largely not deployed settings. We ModBind, novel method for MD simulation-based predictions. ModBind similar accuracy current state-of-the-art methods. Additionally, performs ∼100 times faster than most available or methods, allowing widespread use by modeling community. relative changes primarily useful optimization congeneric series, our requires no structural similarity between ligands, making an absolute predictor koff. is thus tool that can be used virtual screening diverse it distinct from also discuss conditions enable approximate ligand using limitations this approach.

Язык: Английский

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