Faculty of Engineering and Natural Sciences
FENS MAT 551 SEMINARS
Probing Coupled Time Scales and Landscape Shifts in Functional Proteins
Canan Atılgan, Sabancı University
We study the dynamics of folded proteins theoretically, using all-atom and coarse-grained approaches. Our main goal is to understand how functionality is achieved once a protein folds into its three-dimensional structure. In all-atom models, we carry out classical molecular dynamics simulations in water and glycerol at a variety of temperatures, where the protein maintains its structure, but not necessarily its function. We explain the observed relaxation phenomena based on a viscoelastic model, asserting that the protein needs to form concerted interactions with a vicinal layer of solvent. To understand allosteric interactions in which a local change in one part of the protein induces other structural changes in distal parts, we study coarse grained models whereby the protein is considered as a network of its amino acids with links between residues in close proximity. We find that “information” is relayed in the protein through specially optimized pathways. The same principles apply for the commonly utilized interface residues in ligand-receptor interactions. The findings are corroborated by strong evolutionary conservation of key residues along these paths both within single proteins and in interacting ones. Moreover, using coarse-grained models, one may also reproduce residue-by-residue structural changes as determined from the X-ray structures of the ligand-free and ligand-bound forms. The latter is achieved by introducing small perturbations in specific residues, and calculating the changes in the coordinates through linear response theory. These changes are reversible, unless a small ligand that stabilizes certain preferred conformations is also present in the model. The latter observations are explained by shifts in the energy landscapes that are induced by forces, and they cannot be accounted by modifications in temperature or solvent type.
Canan Atılgan received her B.Sc. and Ph.D. degrees in Chemical Engineering from Boğaziçi University in 1991 and 1996, respectively. She was a postdoctoral research fellow at the Supercomputer Computations Research Institute of the Florida State University in 1996 – 1999. She has been a faculty member at Sabancı University since that time. Dr. Atılgan is the recipient of the L'Oréal Turkey For Woman In Science Young Woman Scientist Fellowship (2005), Turkish Academy of Sciences (TUBA), Distinguished Young Scientist Award (2004), The Scientific and Technical Research Council of Turkey (TUBITAK) Encouragement Award (2002), and Bogazici University Ph.D. Thesis Award (1996). Her research interests are centered on the theoretical and computational investigation of complex molecular systems, in particular polymers and proteins. You may visit her web page http://people.sabanciuniv.edu/canan for details on her research.
Wednesday, 28 November 2007, 13:40, FENS G032