Application of enhanced sampling methods in drug design

Abstract

In this thesis I focused my efforts in developing and applying computational approaches aimed to characterize the complex phenomena of molecular recognition, including both kinetic and thermodynamic aspects. In details, I worked on i) prediction of the correct binding mode of small molecules within biological targets of pharmaceutical interest, ii) prediction of the kinetics of protein-ligand unbinding and iii) estimation of covalent drug affinity and reactivity in mutated forms of the targeted protein. Procedures based on the application of enhanced sampling methods are described and employed to solve these challenging tasks.