Semistiff polymer model of unfolded proteins and its application to NMR residual dipolar couplings
ABSTRACT We present a new statistical model of unfolded proteins in which the stiffness of polypeptide backbone is taken into account.
We construct and solve a mean field equation which has the form of a diffusion equation and derive the distribution function
for conformations of unfolded polypeptides. Accounting for the stiffness of the protein backbone results in a more accurate
description of general properties of a polypeptide chain, such as its gyration radius. We then use the distribution function
of a semistiff protein within a previously developed theoretical framework [J. Biomol. NMR 39, 1 (2007)] to determine the nuclear magnetic resonance (NMR) residual dipolar couplings (RDCs) in unfolded proteins. The
calculated RDC profiles (dependence of the RDC value on the residue number) exhibit a more prominent bell-like shape and a
better agreement with experimental data as compared to the previous results obtained with the random flights chain model.
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ABSTRACT: The viscosity dependence of the folding rates for four sequences (the native state of three sequences is a beta-sheet, while the fourth forms an alpha-helix) is calculated for off-lattice models of proteins. Assuming that the dynamics is given by the Langevin equation we show that the folding rates increase linearly at low viscosities \eta, decrease as 1/\eta at large \eta and have a maximum at intermediate values. The Kramers theory of barrier crossing provides a quantitative fit of the numerical results. By mapping the simulation results to real proteins we estimate that for optimized sequences the time scale for forming a four turn \alpha-helix topology is about 500 nanoseconds, whereas the time scale for forming a beta-sheet topology is about 10 microseconds. Comment: 14 pages, Latex, 3 figures. One figure is also available at http://www.glue.umd.edu/~klimov/seq_I_H.html, to be published in Physical Review LettersPhysical Review Letters 05/1997; · 7.73 Impact Factor
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ABSTRACT: Characterization of the unfolded state is a fundamental prerequisite for understanding protein stability and folding. We have investigated local conformational sampling in urea-denatured ubiquitin at pH 2.5 by measuring an extensive set of residual dipolar couplings (RDCs) under conditions of partial molecular alignment. Seven experimental RDCs per peptide unit, including complementary fixed-geometry and interproton (1H(N)-1H(N) and 1H(N)-1H(alpha)) couplings, were used to investigate the structural properties of the peptide chain. Amino-acid-specific potentials that simultaneously reproduce all RDCs in the molecule are found to sample more extended conformations than the standard statistical coil description. Analysis of 3J(HNHalpha) scalar couplings measured under the same conditions suggests that neither polyproline II nor extended beta-regions dominate this additional sampling of extended conformations. Using this approach we propose a model of the conformational landscape throughout the peptide chain of urea-denatured ubiquitin, providing an essential description for understanding the unfolded state.Journal of the American Chemical Society 09/2007; 129(31):9799-807. · 10.68 Impact Factor
Article: The Protein Data Bank[Show abstract] [Hide abstract]
ABSTRACT: The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource. INTRODUCTION The Protein Data Bank (PDB) was established at Brookhaven National Laboratories (BNL) (1) in 1971 as an archive for biological macromolecular crystal structures. In the beginning the archive held seven structures, and with each year a handful more were deposited. In the 1980s the number of deposited structures began to increase dramatically. This was due to the improved technology for all aspects of the crystallographic process, the addition of structures determined by nuclear magnetic resonance (NMR) methods, and changes in the community views about data sharing. By the early 1990s the majority of journals required a PDB accession code and at le...08/2000;