QM/MM Methods: Recent Developments and Application to Membrane Proteins and Molecular Motors

Abstract

I'll briefly discuss recent developments of QM/MM methods in our lab, with an emphasis on methods that allow an efficient sampling of at least local motions coupled to the biochemical process of interest. Next, I'll discuss the application of these methods to address specific mechanistic questions in proton pumps and biomolecular motors. The applications highlight that calibrated QM/MM methods are valuable because they provide not only energetic/kinetic information for the relevant biochemical driving forces (e.g., ATP hydrolysis) in these biomolecular machines but also spectroscopic observables that can be compared directly to experiments. Another feature that emerges from these applications is that changing hydration level of internal protein cavities may play an important role in modulating the proton affinity of key groups and thus the timing of key chemical events. In short, the discussions highlight the advantages of an efficient QM/MM framework based on an approximate DFT method (DFTB3) and the diverse roles of water molecules in biomolecular functions.