Francesco Rao Research Lab

Francesco Rao Research Group

Protein Dynamics

The Protein Folding Network

Proteins are fascinating complex systems. The traditional structure-function paradigm, ``to know function study structure'' which goes back to Watson and Crick, have guided our interpretation of protein function for decades. But our mechanistic understanding of how those processes are regulated is still unclear. It is only rather recently that the possible role of dynamics in signaling, allostery and catalytic activity, per se, has been recognized. The goal of our research is to understand and elucidate the role of dynamics in the context of protein function. To this aim we use the tools of molecular dynamics simulations and complex network analysis to obtain high resolution mappings of the underlying free-energy landscape. The latter, driving the biologically relevant conformational transition, provide a quantitative insight on both the thermodynamics and kinetics of the process.

References:

The Protein Folding Network
F. Rao and A. Caflisch, , J. Mol. Biol. 342, 299, 2004

Complex network analysis of free-energy landscapes
D. Gfeller, P. De Los Rios, A. Caflisch* and F. Rao*, Proc. Nat. Acad. Sci. USA 104, 1817, 2007

Protein dynamics investigated by inherent structure analysis
F. Rao* and M. Karplus*, Proc. Nat. Acad. Sci. USA 107, 9152, 2010

Water Structure and Dynamics

Water Network
There is still an open debate regarding the structure forming capabilities of water at ambient conditions. To probe the presence of such inhomogeneities, we apply complex network analysis methods to a molecular dynamics simulations. Our results indicate the presence of several kinetically inhomogeneous water configurations. Our goal is to understand if and how those inhomogeneities are connected to water anomalies and the central role of water in biology.

References:

Structural Inhomogeneity of Water by Complex Network Analysis
F. Rao*, S. Garrett-Roe, P. Hamm*, J. Phys. Chem. B, 114, 15598, 2010

Three-Dimensional Infrared Spectroscopy of Isotope-Substituted Liquid Water Reveals Heterogeneous Dynamics
S. Garrett-Roe, F. Perakis, F. Rao and P. Hamm*, J. Phys. Chem. B, 115, 6976, 2011

Webdesign by Francesco Rao + Coding by Max Zitelli + 2011