Hue Sun CHAN   Professor

B.Sc., University of Hong Kong, 1981
M.A., University of California at Berkeley, 1983
Ph.D., University of California at Berkeley, 1987
Postdoctoral Fellow, University of California at San Francisco (UCSF), 1987-89
Assistant Research Biophysicist, Assistant Adjunct Professor,
Associate Adjunct Professor
, UCSF, 1989-98
Associate Professor, University of Toronto, 1998-2003
Canada Research Chair, 2001-2010
Professor, University of Toronto, 2003-present

BCH340H -- Proteins: From Structure to Proteomics (Archive)
JBB2026H -- Protein Structure, Folding and Design (offered NOW: Current Fall '14 course outline)

Member of:
CIHR Training Program (at U. of Toronto) in Protein Folding and Interaction Dynamics: Principles & Diseases (Program Advisory Committee)
Editorial Board: Proteins: Structure, Function, and Bioinformatics

Medical Sciences Building, Room 5363

Theoretical and Computational Investigations of Protein Folding, Interactions, and Evolution

Research Synopsis

Moat Landscape: a protein could have a fast-folding throughway process (A) in parallel with a slow-folding process (B) involving a kinetic trap.

From Levinthal to pathways to funnels, Nature Structural Biology, Volume 4, No. 1, January 1997.

Current Research Group Members

Research Group Pictures

U. of Toronto pictures

Biophysics in Canada:
Links to other Canadian biophysics groups (kindly provided by Andrew Rutenberg)

Please see H.S. Chan's departmental page for a more detailed summary & graphical illustrations of his research group's current interests and projects.

Protein folding and interactions are physico-chemical processes. Our group's overall research goal is to elucidate their underlying energetics. To this end, a main emphasis of our effort is to develop proteinlike heteropolymer models with coarse-grained interactions and simplified representations of chain geometries. The rationale of these approaches is to capture the essential physics and at the same time allow for a broad coverage of the protein conformational space -- and also a broad coverage of the sequence space for evolutionary studies -- that is not readily achievable currently in higher-resolution models. Molecular dynamics simulations using common atomic forcefields and explicit water models are used in our work as well, especially for deciphering subtle properties of solvent-mediated interactions. Various combinations of coarse-grained and atomic methods are being used to gain physical insights into general principles of folding, protein interactions, and evolution. The topics we address including folding cooperativity, origin of enthalpic and volumetric folding barriers, nonnative effects in folding, formation of functional and disease-causing dynamic, "fuzzy" complexes involving intrinsically disordered proteins, and conformational switching in protein evolution. Some of these efforts, including investigations into the mathematical basis of the unknotting, decatenating, and supercoil simplifying actions of type-2 topoisomerases, are highlighted in H.S. Chan's departmental webpage (please click here).

Selected Publications
Biophysics of Protein Evolution and Evolutionary Protein Biophysics. T. Sikosek & H.S. Chan J. Royal Soc. Interface 11:20140419 (2014).

Polycation-π Interactions are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family. J. Song, S. C. Ng, P. Tompa, K. A. W. Lee & H. S. Chan, PLoS Comput. Biol. 9(9):e1003239 (2013).

Transition Paths, Diffusive Processes, and Preequilibria of Protein Folding. Z. Zhang & H. S. Chan, Proc. Natl. Acad. Sci. USA 109:20919-20924 (2012).

Evolutionary Dynamics on Protein Bi-Stability Landscapes can Potentially Resolve Adaptive Conflicts. T. Sikosek, E. Bornberg-Bauer & H. S. Chan, PLoS Comput. Biol. 8(9):e1002659 (2012).

Escape from Adaptive Conflict Follows from Weak Functional Trade-Offs and Mutational Robustness. T. Sikosek, H. S. Chan & E. Bornberg-Bauer, Proc. Natl. Acad. Sci. USA 109:14888-14893 (2012).

Cooperativity, Local-Nonlocal Coupling, and Nonnative Interactions: Principles of Protein Folding from Coarse-Grained Models. H. S. Chan, Z. Zhang, S. Wallin & Z. Liu, Annu. Rev. Phys. Chem. 62:301-326 (2011).

Action at Hooked or Twisted-Hooked DNA Juxtapositions Rationalizes Unlinking Preference of Type-2 Topoisomerases. Z. Liu, L. Zechiedrich & H. S. Chan, J. Mol. Biol. 400:963-982 (2010).

Competition Between Native Topology and Nonnative Interactions in Simple and Complex Folding Kinetics of Natural and Designed Proteins. Z. Zhang & H. S. Chan, Proc. Natl. Acad. Sci. USA 107:2920-2925 (2010).

Desolvation Barrier Effects are a Likely Contributor to the Remarkable Diversity in the Folding Rates of Small Proteins. A. Ferguson, Z. Liu & H. S. Chan, J. Mol. Biol. 389:619-636 (2009).

Theoretical and Experimental Demonstration of the Importance of Specific Nonnative Interactions in Protein Folding. A. Zarrine-Afsar, S. Wallin, A. M. Neculai, P. Neudecker, P. L. Howell, A. R. Davidson & H. S. Chan, Proc. Natl. Acad. Sci. USA 105:9999-10004 (2008).

Polyelectrostatic Interactions of Disordered Ligands Suggest a Physical Basis for Ultrasensitivity. M. Borg, T. Mittag, T. Pawson, M. Tyers, J. D. Forman-Kay & H. S. Chan, Proc. Natl. Acad. Sci. USA 104:9650-9655 (2007).

Hydrophobic Association of α-Helices, Steric Dewetting and Enthalpic Barriers to Protein Folding. J. L. MacCallum, M. Sabaye Moghaddam, H. S. Chan & D. P. Tieleman, Proc. Natl. Acad. Sci. USA 104:6206-6210 (2007).

Topological Information Embodied in Local Juxtaposition Geometry Provides a Statistical Mechanical Basis for Unknotting by Type-2 DNA Topoisomerases. Z. Liu, J. K. Mann, E. L. Zechiedrich & H. S. Chan, J. Mol. Biol. 361:268-285 (2006).

Desolvation is a Likely Origin of Robust Enthalpic Barriers to Protein Folding. Z. Liu & H. S. Chan, J. Mol. Biol. 349:872-889 (2005).

Temperature Dependence of Three-Body Hydrophobic Interactions: Potential of Mean Force, Enthalpy, Entropy, Heat Capacity, and Nonadditivity. M. Sabaye Moghaddam, S. Shimizu & H. S. Chan, J. Am. Chem. Soc. 127:303-316 (2005).

Sparsely Populated Folding Intermediates of the Fyn SH3 Domain: Matching Native-Centric Essential Dynamics and Experiment. J. E. Ollerenshaw, H. Kaya, H. S. Chan & L. E. Kay, Proc. Natl. Acad. Sci. USA 101:14748-14753 (2004).

Cooperativity Principles in Protein Folding. H. S. Chan, S. Shimizu & H. Kaya, Methods Enzymol. 380:350-379 (2004).

Origins of Chevron Rollovers in Non-Two-State Protein Folding Kinetics. H. Kaya & H. S. Chan, Phys. Rev. Lett. 90:258104 (2003).

Recombinatoric Exploration of Novel Folded Structures: A Heteropolymer-Based Model of Protein Evolutionary Landscapes. Y. Cui, W. H. Wong, E. Bornberg-Bauer & H. S. Chan, Proc. Natl Acad. Sci. USA 99:809-814 (2002).

Conformational Propagation with Prion-like Characteristics in a Simple Model of Protein Folding. P. M. Harrison, H. S. Chan, S. B. Prusiner & F. E. Cohen, Protein Sci. 10:819-835 (2001).

Folding Alphabets. H. S. Chan, Nature Struct. Biol. 6:994-996 (1999).

Energetic Components of Cooperative Protein Folding. H. Kaya & H. S. Chan, Phys. Rev. Lett. 85:4823-4826 (2010).

Modeling Evolutionary Landscapes: Mutational Stability, Topology and Superfunnels in Sequence Space. E. Bornberg-Bauer & H. S. Chan, Proc. Natl. Acad. Sci. USA 96:10689-10694 (1999).

Protein Folding: Matching Speed and Locality. H. S. Chan, Nature 392:761-763 (1998).

Protein Folding in the Landscape Perspective: Chevron Plots and Non-Arrhenius Kinetics. H. S. Chan & K. A. Dill, Proteins: Struct. Funct. Genet. 30:2-33 (1998).

From Levinthal to Pathways to Funnels. K. A. Dill & H. S. Chan, Nature Struct. Biol. 4:10-19 (1997).
  Click here for an extended list of publications and electronic reprints.

Lectures and seminars

Journal cover images

Meetings organized

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