Physical Chemistry Seminar: Professor Gerhard Stock, University of Freiburg
About the Seminar
"Real time exploration of allosteric communication: Experiment, MD and low-dimensional modeling"
Allostery represents a fundamental mechanism for protein signaling and regulation. While little is known about the underlying dynamical process, recent time-resolved infrared spectroscopy experiments on photoswitchable proteins by Hamm and coworkers have indicated that the allosteric transition occurs on a wide range of timescales (up to ten decades), which suggests a multi-step process on a hierarchical energy landscape. Performing extensive nonequilibrium molecular dynamics simulations for various PDZ domains, the modeling of the experiments reproduces the measured timescales in excellent agreement. To elucidate the underlying mechanism, we consider the time evolution of interresidue contact distances. Using MoSAIC correlation analysis, we identify clusters of highly correlated contacts in various regions of the proteins, which mediate long-range couplings via rigid secondary structure elements. This suggests a model of weakly interacting contact clusters, which reveals that allostery amounts to the propagation of structural and dynamical changes that are genuinely nonlinear and may occur in a non-local fashion. Moreover, the model explains the multiple timescales (from pico- to microseconds) observed in experiment by individual structural subprocess which are coupled in a hierarchical manner.
[1] G. Stock and Peter Hamm, A Nonequilibrium Approach to Allosteric Communication, Phil. Trans. B 373, 20170187 (2018). [2] G. Diez, D. Nagel and G. Stock, Correlation-based feature selection to identify functional dynamics in proteins J. Chem. Theory Comput. 18, 5079 (2022). [3] A. Ali, E. Dorbath, G. Stock, Allosteric communication mediated by protein contact clusters: A dynamical model, J. Chem. Theory Comput. 20, 10731 (2024).
About the Speaker
Gerhard Stock received his diploma in Physics from the Technical University of Munich, Germany. From 1986-1990, he worked as a PhD student at the Department of Chemistry, Technical University of Munich, where he completed his PhD (Prof. W. Domcke) in 1990. 1991-1992 Postdoctoral Fellow (Prof. W. H. Miller) at the Dept. of Chemistry, University of California, Berkeley; 1993-1996 Research Associate, Dept. of Chemistry, Technical University of Munich; 1996 Habilitation (Theoretical Chemistry), Technical University of Munich; 1997-2000 Heisenberg Professor, Dept. of Physics, University of Freiburg; 2000-2009 C4 Professor, Chair of Theoretical Chemistry, University of Frankfurt. Since 2009, Gerhard Stock has been a W3 Professor (Chair of Theoretical Physics) at the University of Freiburg.
Gerhard Stock was awarded the following fellowships and distinctions: 1990 Ph.D. Thesis (summa cum laude); 1991 Postdoctoral Fellowship of the Deutsche Forschungsgemeinschaft (DFG); 1993 Habilitation Fellowship of the Deutsche Forschungsgemeinschaft (DFG); 1997 Heisenberg Prize; 2002 Annual Prize of the International Academy of Quantum Molecular Science. He is a referee and member of referee panels of several funding agencies, including the Deutsche Forschungsgemeinschaft (DFG), Humboldt Foundation, National Science Foundation, Minerva Foundation, and referee for numerous journals, including Science, PNAS, J. Am. Chem. Soc., Phys. Rev. Letters, Rev. Mod. Phys.
Recent activities: 2011/2012 Director of the Institute of Physics at the University of Freiburg; 2013 Co-organizer of the Black Forest Focus on “Protein Dynamics” at the Freiburg Institute for Advanced Studies (FRIAS) and the Telluride Science Research Center meeting on “Vibrationals Dynamics”.
Fields of Research: Ultrafast Nonadiabatic Dynamics and Spectroscopy; Free Energy Landscapes of Biomolecules; Biomolecular Energy flow; Functional Dynamics; Vibrational Signatures of Biomolecular Dynamics.