Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

Probing Macromolecular Mechanics: Heterogeneity and Function

Macromolecular structures underpin all molecular biology, but structures alone do not always tell the whole story. Macromolecules change their conformations in response to their environment and in order to carry out their biological functions. Although these changes reflect their complex structures, they are not always easy to deduce from the structures without further data. Inspired by single molecule experiments on biomolecules, we have been looking for ways of theoretically modeling macromolecular mechanics using both all-atom and coarse-grain representations. In the case of proteins, we have been able to quantify the ease of displacing each amino acid residue within the overall structure. The results show a surprising degree of mechanical heterogeneity and suggest, in particular, that active site residues need to be held carefully in place in order to carry out their functions. This connection is strong enough to make it possible to detect active sites on the basis of their mechanical properties. We have also found that point mutations affecting function can have significant effects of mechanics, including changes distant from the site of the mutations. More generally, internal mechanics may offer an analytical tool for passing more easily from structure to function.

Richard Lavery1, *
Sophie Sacquin-Mora2

1Institut de Biologie et Chimie des Protéines
Département des Biostructures Moléculaires
CNRS UMR 5086 / Université de Lyon
7, passage du Vercors
Lyon 69367, France
2Institut de Biologie Physico-Chimique
Laboratoire de Biochimie Théorique, CNRS UPR 9080
13, rue Pierre et Marie Curie
Paris 75005, France

*Phone: +33 4 72 72 26 37
Fax: +33 4 72 72 26 04
Email: Richard.Lavery@ibcp.fr