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Curvature and Torsion of Protein Main Chain as Local Order Parameters of Protein Unfolding
journal contribution
posted on 2020-05-25, 04:46 authored by Paul Grassein, Patrice Delarue, Adrien Nicolaï, Fabrice Neiers, Harold A. Scheraga, Gia G. Maisuradze, Patrick SenetThermal
protein unfolding resembles a global (two-state) phase
transition. At the local scale, protein unfolding is, however, heterogeneous
and probe dependent. Here, we consider local order parameters defined
by the local curvature and torsion of the protein main chain. Because
chemical shifts (CS’s) measured by NMR spectroscopy are extremely
sensitive to the local atomic environment, CS has served as a local
probe of thermal unfolding of proteins by varying the position of
the atomic isotope along the amino acid sequence. The variation of
the CS of each Cα atom along the sequence as a function
of the temperature defines a local heat-induced denaturation curve.
We demonstrate that these local heat-induced denaturation curves mirror
the local protein nativeness defined by the free energy landscape
of the local curvature and torsion of the protein main chain described
by the Cα–Cα virtual bonds. Comparison between molecular dynamics simulations
and CS data of the gpW protein demonstrates that some local native
states defined by the local curvature and torsion of the main chain,
mainly located in secondary structures, are coupled to each other
whereas others, mainly located in flexible protein segments, are not.
Consequently, CS’s of some residues are faithful reporters
of global protein unfolding, with heat-induced denaturation curves
similar to the average global one, whereas other residues remain silent
about the protein unfolded state. For the latter, the local deformation
of the protein main chain, characterized by its local curvature and
torsion, is not cooperatively coupled to global unfolding.
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heat-induced denaturation curvetorsionC α atomphase transitionheat-induced denaturation curves mirrorprotein nativenessdynamics simulationsorder parametersCS dataNMR spectroscopyprotein segmentsacid sequenceheat-induced denaturation curvescurvaturegpW proteinProtein Main ChainProtein Unfoldingchemical shiftsenergy landscapeLocal Order Parameters
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