Professor, Department of Chemistry and Chemical Biology
Harvard University

Date: Monday, November 6, 2006
Time: 3PM-4PM
Location: BME 1103 (UA Whitaker Building)

"Learning Nature's lessons: what thermal adaptation tells us about principles of protein structure and evolution"

Abstract: Nature uses physical principles of protein stability to adjust to the conditions of the environment and we try to learn how it comes about. First we sought proteomic and genomic signatures of thermal adaptation. By exhaustively enumerating all possible combinations of amino acids we found that composition of seven amino acids - I,V,Y,W,R,E,L - in a proteome serves as a very reliable predictor of organism's Optimal Growth Temperature: correlation between OGT and IVYWREL in all 204 prokaryotes with sequenced genomes and known OGT is R=0.93. In contrast, the common myth that GC content in DNA correlates with OGT does not survive high-throughput scrutiny (R=-0.1). Trying to understand why IVYWREL is such a good predictor of OGT we discovered that Nature uses bothpositive design (i.e. lowering energy of the native conformation) and negative design (raising energy of misfolded conformations). Further, negative design proceeds via strengthening certain specific non-native repulsive interactions. These results have profound implications for understanding correlated mutations and evolution of proteins in general.
In the second part of the talk (time permitting) I will discuss a novel model of microscopic organismal evolution that gives rise to observed Protein Universe.
Additional Information:
Shakhnovich Biophysics Lab at Harvard University

Hosted by: Emmanuel Tannenbaum, School of Biology