CAREER:Free Energies of Protein Partitioning and Membrance Pertubations

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A quantitative measure and molecular-level interpretation of protein-lipid interactions is essential to understand the partitioning, folding and function of membrane-proteins, which make up 20-30% of the human genome. Furthermore, understanding the physical rules that govern the assembly of membranes with their associated proteins is important for future developments in integrated biomembrane nano-devices. Experiment has provided a wealth of valuable information about protein-membrane interaction. Modern computer simulation can complement these experiments, strengthen our microscopic understanding and resolve some unanswered questions. A rigorous statistical mechanical framework is invoked here to capture the free energies governing protein structure and function in a membrane environment. These free energy calculations will push the boundaries of state of the art simulation. Despite the challenges, Dr. Allen has devised a realizable strategy employing polypeptides as model transmembrane segments to elucidate the general mechanisms of protein-lipid interaction. To begin, microscopic simulations will provide a free energy profile of an amino acid, attached to a transmembrane segment, and reveal bilayer perturbations as a function of depth. Such information is unattainable with experiment, yet essential to understand how the stability of a membrane-protein is determined by the specific arrangement of amino acids in the three-dimensional protein structure. The principle of 'hydrophobic matching' has been used to help explain the insertion and folding of proteins, protein activity, lipid micro-domain formation and protein aggregation. Dr. Allen details a series of new and innovative umbrella sampling and free energy perturbation calculations that directly tackle the thermodynamics governing mismatch. Dr. Allen's dedication to university and community is evidenced by his contributions and innovations in teaching and outreach activities. A revamped Computational Chemistry course will tie in both Dr. Allen's previous teaching and current research so that students, theoretical or experimental, learn the skills needed to pursue projects and critically assess published results. Dr. Allen is actively seeking new and exciting ways of harnessing the curiosity and enthusiasm of young and underprivileged students and encouraging them to pursue careers in science. He will co-organize and mentor in the ACS 'SEED' program at UCD which is designed to create opportunities for high school students from economically disadvantaged backgrounds. He is working with the COSMOS program (http://cosmos.ucdavis.edu) to develop a 4-week course suitable for high-school students and is also developing his own initiative, 'Careers in Chemical and Biological Simulation', that will bring together scientists from university and industry to provide students with exciting opportunities in chemical and biological simulation.