Combining simulation and experiments to solve molecular structures

The Voelz lab has been making progress on combining simulation and experiments to solve molecular structures.

Most molecules do not have a single rigid structure in solvent. Instead, they exist in a range of different conformations. Stable proteins exist mostly in the folded conformation, but there is always a small fraction of population that is unfolded. Other molecules may have a very heterogeneous set of conformations, which can make determining their structure in solvent difficult. NMR experiments, for example, can be used for this, but structural information often gets “washed out” due to motional averaging.

Our new method, called BICePs (Bayesian inference of conformational populations) is a robust method to infer the populations of conformational states, using a combination of high-resolution computer modeling and information from experiments. We think BICePs will be very useful for determining the extent to which proteins and other molecules are well-structured in solution. In the future we plan to use it as a tool for designing well-structured mimics of proteins, called peptidomimetics. Our paper describing the new BICePs algorithm has been published in the latest issue of the Journal of Computational Chemistry.