Exploring the Energy Landscape of Proteins for Docking Simulations

Theoretically a protein has a vast number of possible folding paths, which conflicts the short folding time that can be observed in the human body (Levinthal's Paradoxon). However, it can be observed, that all possible states have not the same probability. This motivates to employ Markov State Models, which describe the dynamics of a protein by transition probabilities between metastable sets. We compute these transition probabilities by discretizing the high dimensional phase space with meshfree methods and computing a transition matrix. Based in this technique we can describe the motion of a protein via conformational changes, which allow us to simulate certain classes of protein-ligand docking processes. We close the talk with open questions and future research goals.