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Peter G. Wolynes

Bullard-Welch Foundation Professor of Science, Professor of Chemistry and Materials Science & NanoEngineering, Professor of Physics & Astronomy

The research in my group is broadly concerned with many-body phenomena in biology, chemistry and physics. A major theme is understanding systems where a large diversity of long-lived states is involved, necessitating the use of a statistical characterization of an energy or attractor landscape. The most notable examples are glasses, liquids, biomolecules and biomolecular regulatory networks. In the area of protein folding we are interested both in describing folding kinetics in the laboratory and the development of bioinformatically based schemes for predicting structure from sequence using computer simulation. A key concept is that the energy landscape of a foldable protein looks like a rugged funnel. This idea guides the development of both simple folding kinetics models and structure prediction algorithms. Similar issues of attractor landscapes also arise in higher order biological processes, such as gene recognition and genetic network regulation, which we also study. The energy landscapes of supercooled liquids and glasses also present interesting problems. We have shown how a new approach based on "random first order transitions" explains many quantitative relations found empirically both in liquids and under cryogenic conditions where quantum effects play a role. The same ideas show promise in the study of systems as different as high temperature superconductors, polymer assemblies, and microemulsions. They are also useful for describing the three dimensional structure and dynamics of the interior of living cells.


Wolynes, P. Evolution, Energy Landscapes and the Paradoxes of Protein Folding. Biochimie, 2015 119: 218-230.

Schafer, N. P.; Kim, B. L.; Zheng, W.; Wolynes, P. G. Learning to Fold Proteins Using Energy Landscape Theory. Isr. J. Chem. 2014. 54, 1311-1337. doi:10.1002/ijch.201300145.

H.Truong, B. Kim, N.P. Schafer, P.G. Wolynes, "Funneling and frustration in the energy landscapes of some designed and simplified proteins," J. Chem. Phys.  139:121908, 2013.

A. Davytan, N. Schafer, W. Zheng, C. Clementi, P.G. Wolynes, G.A. Papoian, "AWSEM-MD: Protein structure prediction using coarse-grained physical potentials and bioinformatically based local structure biasing," J. Phys. Chem. 116:9494-8503, 2012.

S. Wang and P.G. Wolynes,  “Active Contractility in Actomyosin Networks,” Proc. Natl. Acad. Sci. USA 109: 6446-6451, 2012.

S. Wang, P.G. Wolynes, "Active patterning and asymmetric transport in a model actomyosin network," J. Chem. Phys. 139:235103-1/11, 2013.

P.G. Wolynes, W.A. Eaton, A. Fersht, “Chemical Physics of Protein Folding,” Proc. Natl. Acad. Sci. USA 109:17770-17771, 2012.

F. Morcos, N.P. Schafer, R.R. Cheng, J.N. Onuchic, P.G. Wolynes, "Coevolutionary information, protein folding landscapes and the thermodynamics of natural selection," Proc. Natl. Acad. Sci. U.S.A.111, 12408-12413.

M. Tsytlonok, P.O. Craig, E. Sivertsson, D. Serquera, S. Perrett, R.B. Best, P.G. Wolynes, L.S. Itzhaki, "Complex energy landscape of a giant repeat protein," Structure, 21:1954, 2013.

Potoyan, D.A; Wolynes, P.G. Dichotomous Noise Models of Gene Switches. J. Chem. Phys. 2015 143:195101.

N.P. Schafer, R.M.B. Hoffman, A. Burger, P.O. Craig, E.A. Komives, P.G. Wolynes, “Discrete Kinetic Models from Funneled Energy Landscape Simulations,” PLOS ONE 7(12):e50635, 2012. [doi:10.137/journal.pone.0050635]

A. Wisitsorasak, P.G. Wolynes, "Dynamical Heterogeneity of the Glassy State," J. Phys. Chem. B118, 7835-7848, 2014.

Tsai, M-Y.; Zheng, W.; Balamurugan, D.; Schafer, N.P.; Kim, B.L.; Cheung, M.S.; Wolynes, P.G. Electrostatics, Structure Prediction and the Energy Landscapes for Protein Folding and Binding. 2015 online publication, Prot. Sci. doi:10.1002/pro.2751.

A. Wisitsorasak and P.G. Wolynes, "Fluctuating mobility generation and transport in glasses," Phys. Rev. E 88:022308, 2013.

W. Zheng, N.P. Schafer, P.G. Wolynes, "Free energy landscapes for initiation and branching of protein aggregation," Proc. Natl. Acad. Sci. .S.A. 110:20515-20520, 2013.

D.U. Ferreiro, E.A. Komives, P.G. Wolynes, "Frustration in Biomolecules," Q. Rev. Biophys. 47, 285-363, 2014.

M. Dzero, J. Schmalian, P.G. Wolynes, "Glassiness in Uniformly Frustrated Systems" in Structural Glasses and Supercooled Liquids" Eds. V. Lubchenko and P.G. Wolynes (John Wiley & Sons, 2012), pp. 193-221.

A. Burger, A. Walczak and P.G. Wolynes,  “Influence of Decoys on the noise and Dynamics of Gene Expression,” Phys. Rev.E. 86:041920-1/7, 2012.

P.O. Craig, J. Lätzer, P. Weinkam, R.M.B. Hoffman, D.U. Ferreiro, E.A. Komives, P.G. Wolynes, "Prediction of native state hydrogen exchange from perfectly funneled energy landscapes" J. Am. Chem. Soc. 133:17463-17472, 2011.

S. Wang and P.G. Wolynes, “Effective temperature and glassy dynamics of active matter,” J. Chem. Phys. 135: 051101/1-4, 2011.

N.P. Schafer, B.L. Kim, W. Zheng, Wolynes, P.G., "Learning to Fold Proteins Using Energy Landscape Theory," Isr. J. Chem. 54, 1311-1337, 2014.

S. Wang and P.G. Wolynes, "Microscopic theory of the glassy dynamics of passive and active network materials," J. Chem. Phys. 138:12A521-1/10, 2013.

P. Rabochiy, P.G. Wolynes, V. Lubchenko, "Microscopically based calculations of the free energy barrier and dynamic length scale in supercooled liquids: The comparative role of configurational entropy and elasticity," J. Phys. Chem. 117:15204-15219, 2013.

Bai, X.; Wolynes, P.G. On the Hydrodynamics of Swimming Enzymes. J. Chem. Phys.  2015, 143, 165101.

A. Wisitsorasak and P.G. Wolynes, “On the Strength of Glasses.” Proc. Natl. Acad. Sci. USA  109:16068-16072, 2012.

Truong, H.H.; Kim, B.L., Schafer, N.P., Wolynes, P.G. Predictive Energy Landscapes for Folding Membrane Protein Assemblies. J. Chem. Phys. 2015, 143, 243101.

W. Zheng, N. Schafer, A Davtyan, G.A. Papoian, P.G. Wolynes, “Predictive Energy Landscapes for Protein-Protein Association,” Proc. Natl. Acad. Sci. USA 109, 19244-19247, 2012.

B.L. Kim, N.P. Schafer, P.G. Wolynes, "Predictive energy landscapes for folding alpha-helical transmembrane proteins," Proc. Natl. Acad. Sci. U.S.A., 111, 11031-11036, 2014.

W. Zheng, N.P. Schafer, P.G. Wolynes, "Frustration in the energy landscapes of multidomain protein misfolding," Proc. Natl. Acad. Sci. USA 110:1680-1685, 2013.

S. Wang and P.G. Wolynes, “On the spontaneous collective motion of active matter,” Proc. Natl. Acad. Sci. USA 108:15184-15189, 2011.

W. Li, P.G. Wolynes, S. Takada, "Frustration, specific sequence dependence and nonlinearity in large-amplitude fluctuations of allosteric proteins," Proc. Natl. Acad. Sci. USA 108: 3504-3509, 2011.

M. Jenik, R. Gonzalo Parra, L.G.Radusky, A.Turjanski, P.G. Wolynes, D.U. Ferreiro, “Protein frustratometer: a tool to localize energetic frustration in protein molecules,"  Nucl. Acids Res., 40: 348-351, 2012.

B. Zhang, P.G. Wolynes, "Stem cell differentiation as a many-body problem," Proc. Natl. Acad. Sci. U.S.A. 111, 10185-10190, 2014.

S. Wang and P.G. Wolynes,  “Tensegrity and Motor-Driven Effective Interactions in a Model Cytoskeleton,” J. Chem. Phys. 136: 145102/1-18, 2012.

H. Lammert, P.G. Wolynes, J.N. Onuchic, "The Role of Atomic Level Steric Effects and Attractive Forces in Protein Folding," Proteins 80:362-372, 2012.

V. Lubchenko and P.G. Wolynes, "Theories of Structural Glass Dynamics: Mosaics, Jamming, and All That" in Structural Glasses and Supercooled Liquids, Eds. V. Lubchenko and P.G. Wolynes (John Wiley and Sons, 2012) pp. 341-379.

Zhang, B.; Wolynes, P.G. Topology, structures, and energy landscapes of human chromosomes. Proc. Natl. Acad. Sci. U.S.A. 2015,  112, 6062-6067.

Sirovetz, B.J.; Schafer, N.P.; Wolynes, P.G. Water Mediated Interactions and the Protein Folding Phase Diagram in the Temperature-Pressure Plane. J. Phys. Chem. B. 2015, 119, 11416-11427.

Papoian, G. A. and Wolynes, P. G. AWSEM-MD: From Neural Networks to Protein Structure Prediction and Functional Dynamics of Complex Biomolecular Assemblies.  Coarse-Grained Modeling of Biomolecules 2017

Lubchenko, V.; Wolynes, P.G. Aging, jamming, and the limits of stability of amorphous solids.  The Journal of Physical Chemistry B 2017

Zheng, W.; Tsai, M.; Wolynes, P.G. Comparing the Aggregation Free Energy Landscapes of Amyloid Beta (1-42) and Amyloid Beta (1-40).  Journal of the American Chemical Society, 113 2017: 11835-11840

Di Pierro, M.; Chang, R.; Aiden, E.; Wolynes, P.G.; Onuchic, J. De Novo Prediction of Human Chromosome Structures: Epigenetic Marking Patterns Encode Genome Architecture.  Proc. Natl. Acad. Sci. USA, 114 2017: 12126-12131

Zhang, B.; Wolynes, P.G. Genomic Energy Landscapes (Biophysical Perspectives).  Biophysical Journal, 112 2017: 427-433

Eaton, W.A.; Wolynes, P.G. Letter: Theory, simulations, and experiments show that proteins fold by multiple pathways.  Proc. Natl. Acad. Sci. USA, 114 2017: E9759-E9760

Sirovetz, B; Wolynes, P.G. Making AWSEM AWSEM-ER by Adding Evolutionary Restraints.  PROTEINS: Structure, Function and Bioinformatics, 85 2017: 2127-2142

Wang, Z.; Potoyan, D. and Wolynes, P.G. Modeling the Therapeutic Efficacy of Synthetic NFκB Decoy Oligodexynucleotides (ODN).  BMC Systems Biology 2017

Chen, M.; Lin, X.; Lu, W.; Onuchic, J.; Wolynes, P.G. Protein Folding and Structure Prediction from the Ground Up II: AWSEM for a/ß Proteins (3473-3482).  J. Phys. Chem. B, 121 2017: 3473-3482

Berrios, E; Gruebele, M; Wolynes, P.G. Quantum Controlled Fusion.  Chem. Phys. Lett., (Special Issue: Ahmed Zewail commemorative issue), 683 2017: 216-221

Potoyan, D.; Bueno, C.; Zheng, W.; Komives, E.A.; Wolynes, P.G. Resolving the NFkB hetero-dimer binding paradox: Strain and frustration guide the binding of dimeric transcription factors.  Journal of the American Chemical Society, 139 2017: 18558-18566

Potoyan, D.; Wolynes, P.G. Stochastic dynamics of genetic broadcasting networks.  Physical Review E, 96 2017

Wang, Z.; Potoyan, D. and Wolynes, P.G. Stochastic resonances in distributed genetic broadcasting networks.  J. Roy. Soc. Interface 2017

Chen, M.; Wolynes, P.G. The Aggregation Landscapes of Huntingtin Exon 1 Protein Fragments and the Critical Repeat Length for the Onset of Huntington’s Disease.  Proc. Natl. Acad. Sci. USA, 144 2017: 4406-4411

Chen, M.; Schafer, N.; Zheng, W. and Wolynes, P.G. The Associative Memory, Water Mediated Structure and Energy Model (AWSEM)-Amylometer: Predicting Amyloid Propensity and Fibril Topology Using an Optimized Folding Landscape Model.  ACS Chemical Neuroscience 2017

Wisitsorasak, A.W.; Wolynes, P.G. The Dynamical Theory of Shear Bands in Structural Glasses.  Proc. Natl. Acad. Sci. USA, 114 2017: 1287-1292

D.U.  Ferreiro, J.A. Hegler, E.A.Komives, and P.G. Wolynes, "On the role of frustration in the energy landscapes of allosteric proteins," Proc. Natl. Acad. Sci. USA 108:3499-3505, 2011.

J. Kurchan, J.S. Langer, T.A. Witten, and P.G. Wolynes, “Scientific Interview” in Dynamical heteroteneities in glasses, colloids, and granular media," Eds. L. Berthier, G. Biroli, j-P Bouchaud, L. Cipelletti and W. van Saarloos (Oxford University Press, 2011) pp. 1-38. [cond.mat arXiv:1010.295v1].

S. Wang, T. Shen, and P.G. Wolynes, "The Interplay of Nonlinearity and Architecture in Equilibrium Cytoskeletal Mechanics," J. Chem. Phys. 134:014510-1-16, 2011.

J.A. Hegler, J. Laetzer, A. Shehu, C. Clementi, and P.G. Wolynes, "Restriction versus guidance in protein structure prediction.” Proc. Natl. Acad. Sci. USA 106:15302-15307, 2009.

D. Ferreiro, J. Hegler, E. Komives, and P.G. Wolynes, "Localizing Frustration in Native Proteins and Protein Assemblies," Proc. Nat. Acad. Sci. USA 104:19819-19824, 2007.

M. Gruebele and P. Wolynes, "Quantizing Ulam's Control Conjecture," Phys. Rev. Lett. 99:060201/1-4, 2007.

P.G. Wolynes, “Energy Landscapes and Solved Protein Folding Problems,” Phil. Trans. Roy. Soc. AA363, 453-464, 2005.

M. Gruebele and P. G. Wolynes, “Vibrational Energy Flow and Chemical Reactions,” Acc. Chem. Res., 37:261-267, 2004.

G.A. Papoian, J. Ulander, M.P. Eastwood, Z. Luthey-Schulten and P.G. Wolynes, "Water in Protein Structure Prediction," Proc. Natl. Acad. Sci. USA 101:3352-3357, 2004.

M. Sasai and P. G. Wolynes, “Stochastic Gene Expression as a Many Body Problem”, Proc. Natl. Acad. Sci. USA, 100:2374-2379, 2003.

V. Lubchenko and P.G. Wolynes, “The Intrinsic Quantum Excitations of Low Temperature Glasses,” Phys. Rev. Lett., 87, 195901, 2001.

X. Y. Xia and P. G. Wolynes, “Fragilities of Liquids Predicted from the Random First Order Transition Theory of Glasses,” Proc. Natl. Acad. Sci. 97(7):2990-2994, 2000.

B. A. Shoemaker, John J. Portman, and Peter G. Wolynes, “Speeding molecular recognition by using the folding funnel: The fly-casting mechanism, Proc. Natl. Acad. Sci. USA 97, 8868-8873, 2000.

J. Bryngelson, J. Onuchic, N. Socci and P. G. Wolynes, “Funnels, Pathways, and the Energy Landscape of Protein Folding: A Synthesis,” Proteins: Structure, Function, and Genetics 21:167-195, 1995.

R. Goldstein, Z. Luthey-Schulten and P. G. Wolynes, “Optimal Protein-Folding Codes from Spin-Glass Theory,”  Proc. Natl. Acad. Sci. USA 89:4918-4922, 1992.

J. D. Bryngelson and P. G. Wolynes, “Spin Glasses and the Statistical Mechanics of Protein Folding,” Proc. Natl. Acad. Sci. USA 84:7524-7528, 1987.

H. Frauenfelder, S. Sligar and P. G. Wolynes, “The Energy Landscapes and Motions of Proteins,” Science 254:1598-1603, 1991.

T. R. Kirkpatrick, D. Thirumalai and P. G. Wolynes, “Scaling Concepts for the Dynamics of Viscous Liquids Near an Ideal Glassy State,” Phys. Rev. A 40(2):1045-1054, 1989.

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  • A.M. Chemistry (1972) Harvard University
  • Ph.D. Chemical Physics (1976) Harvard University
  • A.B. Chemistry (Honors) (1971) Indiana University
  • Department of BioSciences
  • Department of Materials Science and NanoEngineering
  • Department of Physics and Astronomy
  • Institute of Biosciences and Bioengineering
  • Theoretical chemical physics; protein folding and function; glasses and stochastic cell biology
Email: pwolynes@rice.edu
Office: Anderson Biological Laboratories, 302