Physics and Biology of Proteins

Workshop | Monday, June 12, 2017 - Friday, June 30, 2017

Funnels, cooperativity, desolvation, and enthalpic barriers in protein folding (minicourse. Part I)

Monday, June 26, 2017 - 09:30:00 - 10:30:00

Hue Sun Chan

University of Toronto

The Levinthal paradox of protein folding is commonly perceived as
stating the impossibility of folding by a completely random
search. Often missed, however, is the historical context: The
question raised by Levinthal was in response to the experimental
discovery of two-state, switch-like cooperative folding in the
late 1960s, rather than to the problem of conformational search
per se [1]. The physical implication of this understanding on the
notion of a funnel-like energy landscape will be discussed.
Principles governing cooperative folding can be gleaned from
coarse-grained models. Comparisons between theory and experiment
on cooperative folding indicate a prominent role of desolvation
barriers [2]. Investigations into the role of desolvation in protein
folding resolves an apparent inconsistency between experimental
observations of enthalpic folding barriers and the theoretical
funnel picture of folding [1,3]. Examples will be given to illustrate
how important folding principles have been gleaned from studies
using native-centric models, including a critical assessment of
the diffusion perspective of folding and the concept of
preequilibrium [4,5].

[1] Chan, Zhang, Wallin & Liu (2011) Annu Rev Phys Chem 62:301-326
[2] Chen & Chan (2014) PCCP 16:6460-6479
[3] MacCallum, Sabaye Moghaddam, Chan & Tieleman (2007) PNAS 104:6206-6210
[4] Zhang & Chan (2012) PNAS 109:20919-20924
[5] Hu, Chen, Wang, Chan & Zhang (2017) PCCP 19:13629-13639