6-8 Title: Packing in Protein Cores

报告题目:Title: Packing in Protein Cores

报  告 人:Prof. Corey O'Hern   Yale University

报告时间:  6月8日 10:30


联  系 人:魏冬青 34204573, This e-mail address is being protected from spambots. You need JavaScript enabled to view it.

徐沁 34204348, This e-mail address is being protected from spambots. You need JavaScript enabled to view it.



Proteins are biological polymers that play important roles in cellular processes ranging from the purely structural to the actively catalytic. It is well-established that a large contribution to protein stability originates from the sequestration from solvent of hydrophobic residues in the protein core. How are such hydrophobic residues arranged in the core; how can one best model the packing of these residues, and are residues loosely packed with multiple allowed side chain conformations or densely packed with a single allowed side chain conformation? We have shown that it is possible to recapitulate the side chain dihedral angle distributions observed in protein crystal structures using a hard-sphere model with stereochemical constraints and explicit hydrogen atoms. Using Voronoi partitioning of the protein core, these studies have shown that protein cores possess packing fractions ϕ ≈ 0.56, which is significantly less than the value of 0.74 that has been quoted in the literature for nearly 40 years. We have also been shown that, for a given protein core, there are no alternative arrangements of the same amino acids that are consistent with a well-packed core with no atomic overlaps. This also holds true for mutations to protein cores. These results emphasize that are only a small number of combinations of core residues that can properly fit within a given protein core. We believe that studies of packing of side chains in protein cores and at protein-protein interfaces can inform mutation and design studies of proteins.



Corey O’Hern joined the faculty of the School of Engineering and Applied Science at Yale with joint appointments in the Department of Mechanical Engineering & Materials Science (MEMS), Applied Physics, Physics, and Graduate Program in Computational Biology & Bioinformatics (CBB) in July 2002 after postdoctoral fellowships in physics at the University of Chicago and the University of California, Los Angeles.  My research group, which currently consists of twelve graduate students and three postdocs, tackles a broad range of fundamental questions in soft matter and biological physics using a combination of theoretical and computational techniques.  In soft matter, the group seeks a predictive understanding of glass and jamming transitions, in which materials such as granular media and dense colloidal suspensions, develop solid-like properties in the absence of crystallization over a narrow range of control parameters.  In the area of biological physics, my group is interested in computational protein design and structure prediction, crowding and sub-diffusive motion in the cell cytoplasm, applying machine learning approaches to large biomedical data sets, and modeling tissue development and cancerous tumor growth. Prof. O’Hern’s research has been funded by the National Science Foundation‚ Army Research Office, Defense Threat Reduction Agency, Defense Advanced Research Projects Agency, National Institutes of Health, and the W. M. Keck Foundation. He has authored more than 100 manuscripts in peer-reviewed journals and given more than 150 seminars, colloquia, and presentations at universities and scientific meetings in the US and abroad. He has served in a number of leadership positions in the US soft matter research community, including the Chair of the Topical Group on Statistical and Nonlinear Physics of the American Physical Society.  He is a co-founder of the Integrated Graduate Program in Physical and Engineering Biology (IGPPEB), which provides graduate training for Ph.D. students that seek to pursue research at the interface of biology, physics, and engineering, and serves on the Executive Committee for the Raymond & Beverly Sackler Institute (RBSI) for Biological, Physical, and Engineering Sciences at Yale.