Title: Rare Conformational Transitions in Biomolecular Systems
Abstract:
Classical molecular dynamics (MD) simulations based on atomic models play an increasingly important role in a wide range of applications in physics, biology and chemistry. One of the most difficult problems is the characterization of large conformational transitions occurring over long-time scales. A significant challenge is to sample the transitions between metastable states associated with slow molecular processes. Most computational strategies require the knowledge of a suitable reaction-coordinate, which have traditionally been constructed using human intuition. To tackle increasingly difficult problems, it is important to develop more objectively robust approaches. Transition path theory, combining free energy methods, string method, transition pathway techniques, stochastic Markov State Models, and Machine Learning techniques based on artificial Neural Networks, offers a powerful paradigm to address these issues.1-6 These concepts will be formally introduced and illustrated with a few recent computational studies of biomolecular systems.
References
1. A. C. Pan, D. Sezer & B. Roux. Finding transition pathways using the string method with swarms of trajectories, J. Phys. Chem. B 112, 3432-3440, (2008).PMC2674374
2. A. C. Pan & B. Roux. Building Markov state models along pathways to determine free energies and rates of transitions, J. Chem. Phys. 129, 064107, (2008).PMC2674374
3. B. Roux. String Method with Swarms-of-Trajectories, Mean Drifts, Lag Time, and Committor, J. Phys. Chem. A 125, 7558-7571, (2021)
4. B. Roux. Transition rate theory, spectral analysis, and reactive paths, J. Chem. Phys. 156, 134111, (2022)
5. Z. He, C. Chipot & B. Roux. Committor-Consistent Variational String Method, J. Phys. Chem. Lett. 13, 9263−9271, (2022)
6. H. Chen, B. Roux & C. Chipot. Discovering Reaction Pathways, Slow Variables, and Committor Probabilities with Machine Learning, Journal of chemical theory and computation 19, 4414-4426, (2023)
Bio:
Benoit Roux was born in the city of Montreal, Canada, in 1958. In 1981, he received a B.Sc. in Physics from the University of Montreal, followed by a M.Sc. in Biophysics in 1985 under the supervision of Remy Sauve. In 1990, he obtained a Ph.D. in Biophysics from Harvard University under the direction of Martin Karplus. He has previously held positions in the Physics Department at the University of Montreal and in the Biophysics Department at the Weill Medical College of Cornell University. Since 2005, he has been at the University of Chicago where he is the Amgen Professor of Biochemistry and Molecular Biology and Professor in the Chemistry Department. Also, he currently holds a joint appointment at Argonne National Laboratory where he is Senior Computational Biologist. An important focus of his laboratory is the understanding of the structure and function of ion channels. He is particularly interested in issues about ion permeation, ion selectivity, gating, and channel inhibitors. He also has a considerable effort aimed at understanding the microscopic factors regulating Src family of tyrosine kinases that play a critical role in the onset of cancer. His research on tyrosine kinases encompasses a combination of experimental and computational approaches to achieve a more complete understanding of Src activation. He is one of the developers of the programs CHARMM and NAMD, and a co-developer of the polarizable Drude force field in collaboration with Alex MacKerell from University of Maryland.
In 1998, he was awarded the Rutherford Medal from The Royal Society of Canada and the Noranda Lecture Award from The Chemical Institute of Canada for his work. In 2013, he was elected Fellow of the Biophysical Society. In 2016, he was elected Fellow and National Lecturer of the Biophysical Society of Canada. In 2021 he was elected member of The Royal Society of Canada. In 2024 he was elected Fellow of the American Association for the Advancement of Science (AAAS).
Google Scholar: https://scholar.google.com/citations?user=hoGTGlMAAAAJ&hl=en.
Wikipedia : https://en.wikipedia.org/wiki/Benoît_Roux
Keywords: Ion channels, pumps, kinases, transport