Lessons from Nature on Molecular Engineering

When: Thursday, November 15, 2012 at 4:00 pm
Where: DA 114
Speaker: Dr. Gevorg Grigoryan
Organization: Dartmouth College
Sponsor: Physics Colloquium

Living cells owe much of their abilities to biological macromolecules, such as proteins. These molecules spontaneously fold into complex structures and super-structures, allowing them to perform chemical catalysis, generate mechanical force, and sense the environment. Such self-assembling functional molecules are highly attractive as we aim to control events at the atomic level and develop novel therapeutics. Therefore, learning the natural design principles of these “smart” molecules, and learning to engineer new ones with desired properties is of critical importance. I will describe several undertakings aiming to address these goals. 1) An essential role for cellular proteins is the recognition of “correct” from “incorrect” interaction partners. In an effort to understand this process, we have designed peptide-binding partners for human bZIP transcription factors that selectively recognize just one out of 20 closely related bZIP families. 2) The universe of natural protein structures consists of highly recurring structural motifs, one reason for which is the designability of these motifs – the relative ease with which they can be stabilized with natural amino acids. Using a novel computational method to rapidly quantify designability, we have engineered peptides that self-assemble into a pre-defined structural array around single-walled carbon nanotubes. Furthermore, we have shown that designability is a highly effective general filter, capable of readily delineating incorrect regions in predicted structures of natural proteins, without knowing the correct answer.


“Computational Design of Virus-like Protein Assemblies on Carbon Nanotube Surfaces”, G. Grigoryan, Y. H. Kim, R. Acharya, K. Axelrod, R. M. Jain, L. Willis, M. Drndic, J. M. Kikkawa, and W. F. DeGrado, Science, 332(6033): 1071-1076, 2011

“Design of Protein-interaction Specificity Gives Selective bZIP-binding Peptides”, G. Grigoryan, A. W. Reinke, and A. E. Keating, Nature458: 859-864, 2009

Host: Assistant Professor Meni Wanunu