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. 2015 Nov 19;119(46):14622-30.
doi: 10.1021/acs.jpcb.5b08619. Epub 2015 Nov 10.

Sequence- and Temperature-Dependent Properties of Unfolded and Disordered Proteins from Atomistic Simulations

Gül H Zerze  1 , Robert B Best  2 , Jeetain Mittal  1
Affiliations

Sequence- and Temperature-Dependent Properties of Unfolded and Disordered Proteins from Atomistic Simulations

Gül H Zerze et al. J Phys Chem B. .

Abstract

We use all-atom molecular simulation with explicit solvent to study the properties of selected intrinsically disordered proteins and unfolded states of foldable proteins, which include chain dimensions and shape, secondary structure propensity, solvent accessible surface area, and contact formation. We find that the qualitative scaling behavior of the chains matches expectations from theory under ambient conditions. In particular, unfolded globular proteins tend to be more collapsed under the same conditions than charged disordered sequences of the same length. However, inclusion of explicit solvent in addition naturally captures temperature-dependent solvation effects, which results in an initial collapse of the chains as temperature is increased, in qualitative agreement with experiment. There is a universal origin to the collapse, revealed in the change of hydration of individual residues as a function of temperature: namely, that the initial collapse is driven by unfavorable solvation free energy of individual residues, which in turn has a strong temperature dependence. We also observe that in unfolded globular proteins, increased temperature also initially favors formation of native-like (rather than non-native-like) structure. Our results help to establish how sequence encodes the degree of intrinsic disorder or order as well as its response to changes in environmental conditions.

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Figures

Figure 1:
Figure 1:
Top left: Uversky diagram of IDPs and globular proteins, Top right: Das and Pappu diagram of IDPs; symbols indicate peptides studied in this work. Bottom: Ensemble averaged intra-chain distance (Rij) profiles of the polypeptides with respect to chain separation. Theoretical polymer scaling limits are shown with dashed lines.
Figure 2:
Figure 2:
Radius of gyration (Rg) of peptides (left) and secondary structures defined by dssp algorithm, Middle column: Coil fraction assigned by dssp, Right column: α -helix and β-sheet fractions. Dashed thick lines: Total data averages, solid lines with error bars: narrow Rg based-window averages, Rg-windows: 1.2-1.3 nm for CSP and IN, 1.3-1.4 nm for LR, 2.0-2.1 nm for PROT-C, 1.6-1.7 nm for PROT-N. Rg interval represented here is selected differently for different proteins to consider commonly sampled Rg in all temperatures for different proteins. Error bars are blocked standard errors using ten equal non-overlapping blocks.
Figure 3:
Figure 3:
Rg-window averages normalized solvent accessible surface area (⟨SASA⟩) of each amino acid in each peptide. Rg windows are the same as in Figure 2 (secondary structures). Error bars are blocked standard errors using four equal non-overlapping blocks.
Figure 4:
Figure 4:
Intra-chain distance (Rij) profiles of the peptides with respect to chain separation at different temperatures.
Figure 5:
Figure 5:
Comparison of properties at different temperatures at same Rg. A. Selected temperature couples are indicated on Rg change plot, B. Rg distribution of couples, black: low-T, red: high-T, green: average Rg C. Secondary structure propensities per residue black: low-T, red: high T, D. Backbone contacts of couples, upper triangle: low-T, lower triangle: high-T.
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