Title: "Energy Landscapes From Glasses to the Intelligence of Biomolecules"

Peter Wolynes, Professor of Chemistry, BioSciences, Materials Science & NanoEngineering, and Physics and Astronomy

Rice University

Hosted by: Davit Potoyan & Xueyu Song

Abstract: The notion of energy Landscapes informs work ranging from cosmology to neurology. The theory of energy landscapes has been most quantitatively developed in the “middle realm” from materials to biomolecules. I will first describe how the energy landscapes of glasses are now so well understood as to provide amazingly quantitative predictions.

The energy landscape theory of protein folding and machine learning/artificial intelligence have a long common history.

Starting in the late 1980’s energy landscape ideas suggested that efficient folding required the selection of funneled landscapes. This insight powered the design of structure prediction codes using bioinformatic input and the success of such codes has grown over the decades. A decade ago a great leap in accuracy was achieved when the explosion of sequencing efforts enabled the efficient use of co-evolutionary analysis in machine learning. The physical and evolutionary energy landscapes are correlated. Evolutionary selection however requires not only funneled folding landscapes but also frustrated parts of the landscape that allow functional binding to targets and allosteric motions. This functional frustration shows up in the co-evolutionary analysis and improves structural predictions over what can be done based on a single sequence. 

I will discuss how the analysis of frustration gives insights both into the evolution and the de-evolution of proteins and the exon-intron problem. Frustration analysis can also empower machine learning tools such as Alphafold to not just predict static structures but also to uncover functional pathways of protein motion. Energy landscape ideas also provide new tools for drug design.

Bio: Peter Wolynes is the D.R. Bullard-Welch Foundation Professor of Science, with appointments in the departments of Chemistry, Physics and Astronomy, BioSciences and Materials Science and Engineering at Rice University.  He graduated with an A.B. from Indiana University in 1971 and received a Ph.D. in Chemical Physics from Harvard University in 1976. He spent most of the year as a postdoctoral fellow with John Deutch at the Massachusetts Institute of Technology. He then spent from Fall 1976 to 1979 as an Assistant Professor in the Chemistry department at Harvard. In 1980 he moved to the University of Illinois, eventually becoming the Center for Advanced Study Professor of Chemistry, Physics and Biophysics. In 2000 he moved to the Department of Chemistry and Biochemistry at the University of California, San Diego. In 2011 he was named D.R. Bullard-Welch Foundation Professor of Science, with appointments in the departments of Chemistry, Physics, Biosciences and Materials Science and Engineering at Rice University in Houston, Texas.
 
Professor Wolynes has been a visiting scholar for extended periods at the Max Planck Institute for Biophysical Chemistry, the Institute for Theoretical Physics (UCSB), the Institute for Molecular Science (Okazaki, Japan) and the Ecole Normale Superieure (Paris, France). He was a Fogarty Scholar-in-Residence at the National Institute of Health, Hinshelwood Lecturer at Oxford, and the Linnett Visiting Professor at Cambridge.
 
Wolynes’s work across the spectrum of theoretical chemistry and biochemistry has been recognized by the 1986 ACS Award in Pure Chemistry, the 2000 Peter Debye Award for Physical Chemistry of the ACS, the Fresenius Award, the Joseph Hirschfelder Prize and the ACS Award in Theoretical Chemistry 2012. For his work on the energy landscape theory of protein folding he received the 2004 Biological Physics Prize from the American Physical Society (now called the Max Delbrück Prize) and the 2008 Founders Award of the Biophysical Society. He received an honorary Doctor of Science from Indiana University in 1988 and an honorary doctorate from Stockholm University in 2010.  He was elected to both the National Academy of Sciences and the American Academy of Arts and Sciences in 1991. He is a fellow of the American Association for the Advancement of Science, the American Physical Society and the Biophysical Society. Wolynes has been elected to the American Philosophical Society, the German Academy of Sciences "Leopoldina," and as a Foreign Member to the Royal Society of London and the Indian National Science Academy. He was named an Einstein Chair Professor of the Chinese Academy of Sciences in 2010.