Physics and Biology of Proteins

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

Volumetric effects of elementary hydrophobic interactions on pressure-dependent protein folding (minicourse. Part III)

Wednesday, June 28, 2017 - 09:00:00 - 10:00:00

Hue Sun Chan

University of Toronto

Following a brief historical review of the subject matter, I'll present
pertinent findings from my group that started with explicit-water atomic
simulations of volumetric effects of hydrophobic solvation [1] and
association [2] that serve to clarify the central role of cavities (voids)
in pressure-dependent behaviors of nonpolar solutes in water [2,3]. Based
on results from this work, an implicit-water atomic chain model has
recently been developed to embody effects of the particulate nature of
water and energetics of solvation on a polypeptide. The model was tested
by Langevin dynamics simulations of a short polyalanine. Consistent with
prior experiment [4], coil-helix transition in our simulation is associated
with an average volume decrease; but the transition process nonetheless
entails a robust positive activation volume. Thus pressure likely
stabilizes helices of short peptides but is expected to slow down their
formation [5]. General ramifications of our theoretical findings for
pressure effects on globular protein folding, including the origins of
volume barriers, will also be explored.

[1] Sabaye Moghaddam & Chan (2007) J Chem Phys 126:114507
[2] MacCallum, Sabaye Moghaddam, Chan & Tieleman (2007) PNAS 104:6206-6210
[3] Dias & Chan (2014) J Phys Chem B 118:7488-7509
[4] Neumaier, Buttner, Bachmann & Kiefhaber (2013) PNAS 110:988-993
[5] Krobath, Chen & Chan (2016) Biochemistry 55:6269-6281