Professor John E. Straub at Boston University is supported by an award from the Chemical Theory, Models and Computational Methods (CTMC) Program in the Chemistry Division to perform theoretical and computational research on predictions of the structure of the lipid membrane. The lipid membrane plays a key role in the organization and function of the cell. The systematic investigation of lipid membranes is essential to our understanding of fundamental aspects of cellular function, including cellular transport and signaling. At the present time, state-of-the-art computational models fail to capture key aspects of membrane structure and function. The Straub group is developing novel theoretical models of membrane and membrane proteins that aspire to a new level of realism in the computational modeling of the cell. As such, the successful development of the methods and their applications may be transformative to the field. This project includes the training and mentoring of undergraduate and graduate research students as well as the development of simulation methods, codes, and datasets. A complete textbook on the topic "Mathematical Methods for Chemists" is being developed that will be made freely available to instructors and students.
The program of analyzing multi-component protein mixtures partitioning with lipid domains in heterogeneous membrane surface structure is extremely challenging. For direct comparison with experiment, it is necessary to perform all-atom simulations, so the free energy calculations use Umbrella Sampling and Energy Representation methods for speed and accuracy and Simulated Tempering in dihedral space and free volume space for enhanced conformational sampling. The multi-component mixtures are complex, containing cholesterol, sphingolipids, glycolipids and other agents important in determining lipid phase domains. The goal of this research is to enable the first de novo studies of membrane domain formation and membrane protein partitioning using atomistic models. The models are validated against average experimental measurements of nanoscopic membrane structures in membrane mixtures and protein partitioning between lipid domains.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
