Understanding biomolecular dynamics using molecular simulations

 

Our research is concerned with the dynamics of large biomolecules, in particular with protein dynamics, folding and binding. Through the impressive achievements of structural biology, much has been learnt about the function of proteins by solving the structures of their stable states (e.g. active, inactive conformations). Studying the dynamics and mechanism of transitions between these states is still a major challenge for both experiment and simulation, yet is equally important for understanding function. We develop novel methods for studying macromolecular dynamics and apply them to biologically interesting systems, using a combination of simulation and theory appropriate for addressing each question.

For example, we have devised algorithms for enhanced sampling of the "rare events" in simulations, which constitute the reactive portions of the trajectory. By designing good "reaction coordinates", we are able to describe the progress of the reaction (mechanism) quantitatively. A particular focus of our current work is the development of coarse-grained models, whose reduced complexity permits us to study larger systems on longer time scales than would otherwise be possible. Making a connection with experimental results through collaborations is very important, either by using theory to help in interpreting experiments or experimental data to refine simulation methodology. We have used coarse- grained models to help interpret single molecule protein folding experiments based on fluorescence resonance energy transfer or atomic force microscopy and all-atom models to interpret NMR dynamics experiments.