Computational Molecular Design: Mathematical Theory, High Performance Computing, In Vivo Experiments

Abstract. Molecular dynamics and related computational methods enable the description of biological systems with all-atom detail. However, these approaches are limited regarding simulation times and system sizes. A systematic way to bridge the micro-macro scale range between molecular dynamics and experiments is to apply coarse-graining (CG) techniques. We will discuss Markov State Modelling, a CG technique that has attracted a lot of attention in physical chemistry, biophysics, and computational biology in recent years. First, the key ideas of the mathematical theory and its algorithmic realization will be explained, next we will discuss the question of how to apply it to understanding ligand-receptor binding, and last we will ask whether this may help in designing ligands with prescribed function. All of this will be illustrated by telling the story of the design process of a pain relief drug without concealing the potential pitfalls and obstacles.