Proteins are an integral part of nature’s material design. Here we apply
multiscale modeling capable of providing a bottom-up description of the
nanomechanics of chemically complex protein materials under large deformation
and fracture. To describe the formation and breaking of chemical bonds of
different character, we use a new reactive force field approach that enables
us to describe the unfolding dynamics while considering the breaking and
formation of chemical bonds in systems that are comprised of several thousand
atoms. We particularly focus on the relationship between secondary and
tertiary protein structures and the mechanical properties of molecules under
large deformation and fracture. Our research strategy is to systematically
investigate the nanomechanics of three protein structures with increasing
complexity, involving alpha helices, random coils and beta sheets. The model
systems include an alpha helical protein from human vimentin, a small protein
-conotoxin
PnIB from
conus pennaceus, and lysozyme, an enzyme that catalyzes breaking of
glycosidic bonds. We find that globular proteins can feature extremely long
unfolding paths of several tens of nanometers, displaying a characteristic
sawtooth shape of the force-displacement curve. Our results suggest that the
presence of disulfide cross-links can significantly influence the mechanics of
unfolding. Fibrillar proteins show shorter unfolding paths and continuous
increase of forces until molecular rupture occurs. In the last part of the
article we outline how a mesoscale representation of the alpha helical protein
structure can be developed within the framework of hierarchical multiscale
modeling, utilizing the results of atomistic modeling, without relying on
empirical parameters. We apply this model to describe the competition between
entropic and energetic elasticity in the mechanics of a single alpha helical
protein molecule, at long time scales reaching several microseconds. We
conclude with a discussion of hybrid reactive-nonreactive modeling that could
help to overcome some of the computational limitations of reactive force
fields.
Laboratory for Atomistic and
Molecular Mechanics
Department of Civil and Environmental Engineering
Massachusetts Institute of Technology
77 Massachusetts Ave., Room 1-272
Cambridge, MA 02139
United States
