Molecular modeling of conformational dynamics and its role in enzyme evolution

With increasing computational power, biomolecular simulations have become an invaluable tool for understanding enzyme mechanisms and the origins of enzyme catalysis. More recently, computational studies have started to focus on understanding how enzyme activity itself evolves, both in terms of enhancing the native or new activities on existing enzyme scaffolds, or completely de novo on previously non-catalytic scaffolds. In this context, both experiment and molecular modeling provided strong evidence for an important role of conformational dynamics in the evolution of enzyme functions. This contribution will present a brief overview of the current state of the art for computationally exploring enzyme conformational dynamics in enzyme evolution, and, using several showcase studies, illustrate the ways molecular modeling can be used to shed light on how enzyme function evolves, at the most fundamental molecular level.