Bioinformatics Seminar -- Professor George Makhatadze presents "Proteins Stabilized to Order" April 10, 2009
April 10, 2009 at 2pm in Cameron 101, the BRC and CRI will host Prof. George Makhatadze, Professor of Biology, Rensselaer Polytechnic Institute. "Proteins Stabilized to Order" will be presented.
Professor George Makhatadze
Professor of Biology
Chaired Constellation Professor in Biocomputation and Bioinformatics
Rensselaer Polytechnic Institute
http://www.rpi.edu/dept/bio/faculty/profiles/makhatadze.html
April 10, 2009 UNC Charlotte, Cameron 101 at 2pm
"Proteins Stabilized to Order"
The ability to design stable proteins is of great importance to biotechnology and other industries. In order to design or engineer proteins with increased stability it is necessary to have a fundamental understanding of the intramolecular forces that contribute to stabilizing the native conformation. The progress in understanding the forces responsible for the protein stability has been enormous, largely through the combination of experimental and theoretical approaches. The protein core is stabilized by hydrophobic interactions between buried nonpolar side chains. Burial of polar residues in the core is unfavorable due to the high energetic cost of desolvation, however, this energetic penalty can be offset by forming hydrogen bonds with other polar groups or buried water molecules. The core residues are further stabilized by van der Waals (packing) interactions. Hydrogen bonding and packing interactions in the protein core have been demonstrated to be as important as hydrophobicity for stability. All these interactions occur in the protein interior. The role of surface residues for protein stability received much less attention. It was believed that surface residues are not important for protein stability particularly because their interactions with the solvent should be similar in the native and unfolded states. Recent experiments in my laboratory have shown that surface residues are also important in modulating the stability of a protein. I will discuss in details our method for protein stabilization that uses rational design of surface charge-charge interactions. In addition, I will give several examples providing experimental validation for this computational protein design approach.
