Using molecular dynamics (MD) simulations to study the kinetics of drug unbinding is a desirable but difficult task primarily due to the extremely long timescales involved. Recent progress in enhanced sampling methods, including the development of the approaches Infrequent Metadynamics and SGOOP, makes it possible to address this and a range of related problems with full atomistic resolution, reaching timescales previously unattainable in MD simulations. In this talk, I will discuss the key principles behind these approaches. I will then highlight some applications calculating pathways, timescales and rate-determining steps of ligand unbinding in various systems including an FDA-approved anti-cancer drug as it unbinds from host kinase.

How and when does a drug leave the binding pocket of a host protein

253rd National Meeting (2017)

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