Using Biomolecular Simulations to Explore Protein Mechanisms

Biomolecules are intrinsically dynamic. By undergoing motions on a wide range of time and length scales, they are able to bind to a diverse array of substrates, regulate their own activities, and transmit information over considerable distances. Dynamic properties therefore play a key role in protein and nucleic acid molecules and add a third facet to the traditional structure/function relationship. In this talk, Wereszczynski will describe how his lab has used molecular dynamics simulations to explore the link between dynamics and mechanisms, with a particular focus on two systems. First, the effects of the histone variants macroH2A and H2A.Z on the nucleosome core particle will be discussed. Results show that modifications at the L1 loops affect DNA stability and alter dynamics networks throughout the complex. Second, simulations of the pilin assembling class C sortase (SrtC) enzymes in Streptococcus pneumonia will be presented. Both computational and experimental results demonstrate that the wildtype SrtC enzyme is surprisingly rigid, even out to long timescales, and that mutations which increase flexibility strongly correlate with increased in vitro catalytic activity.