Free Energy Determinants of Secondary Structure Formation: III. β-Turns and their Role in Protein Folding

Yang, An‐Suei; Hitz, Benjamin

doi:10.1006/jmbi.1996.0364

Cited by 108 publications

(91 citation statements)

References 36 publications

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“…Indeed, previous work from our lab has argued that electrostatic forces are net destabilizing~Yang & Honig, 1995a& Honig, , 1995bYang et al, 1996!. In this paper we are comparing two compact conformations and arguing that electrostatic forces are optimized in the native structure relative to other alignments or topologies rather than to a hypothetical unfolded state.…”

Section: Table 5 Individual Charge-charge (C0c) and Charge-dipole (Cmentioning

confidence: 85%

Free energy determinants of tertiary structure and the evaluation of protein models

Petrey

Honig

2000

Protein Science

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We develop a protocol for estimating the free energy difference between different conformations of the same polypeptide chain. The conformational free energy evaluation combines the CHARMM force field with a continuum treatment of the solvent. In almost all cases studied, experimentally determined structures are predicted to be more stable than misfolded "decoys." This is due in part to the fact that the Coulomb energy of the native protein is consistently lower than that of the decoys. The solvation free energy generally favors the decoys, although the total electrostatic free energỹ sum of Coulomb and solvation terms! favors the native structure. The behavior of the solvation free energy is somewhat counterintuitive and, surprisingly, is not correlated with differences in the burial of polar area between native structures and decoys. Rather, the effect is due to a more favorable charge distribution in the native protein, which, as is discussed, will tend to decrease its interaction with the solvent. Our results thus suggest, in keeping with a number of recent studies, that electrostatic interactions may play an important role in determining the native topology of a folded protein. On this basis, a simplified scoring function is derived that combines a Coulomb term with a hydrophobic contact term. This function performs as well as the more complete free energy evaluation in distinguishing the native structure from misfolded decoys. Its computational efficiency suggests that it can be used in protein structure prediction applications, and that it provides a physically well-defined alternative to statistically derived scoring functions.

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Section: Table 5 Individual Charge-charge (C0c) and Charge-dipole (Cmentioning

confidence: 85%

Free energy determinants of tertiary structure and the evaluation of protein models

Petrey

Honig

2000

Protein Science

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“…Isolated oligopeptide sequences, which have -turn conformation in their proteins of origin, are often found to adopt unordered structures. [18][19][20] This suggests that tertiary interactions of the neighboring polypeptide regions play an important role in stabilizing -turns in proteins and therefore, experimental characterization of -turns in linear sequences involves many difficulties. Free energy calculations showed that the energy difference between the extended and the -turn conformation of oligopeptides is negligible and even that extended structure is favored.…”

Section: Introductionmentioning

confidence: 99%

“…Free energy calculations showed that the energy difference between the extended and the -turn conformation of oligopeptides is negligible and even that extended structure is favored. 20 In solvents with low dielectric constants which, instead of solvating amide C¼ ¼O and NÀ ÀH groups, induce intramolecular interactions, short peptides usually adopt -turn structures more readily than in aqueous media. The use of such solvents could also compensate for the absence of a protein environment.…”

Section: Introductionmentioning

confidence: 99%

Optical spectroscopic elucidation of β‐turns in disulfide bridged cyclic tetrapeptides

2006

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Vibrational circular dichroism (VCD) spectroscopic features of type II β‐turns were characterized previously, but, criteria for differentiation between β‐turn types had not been established yet. Model tetrapeptides, cyclized through a disulfide bridge, were designed on the basis of previous experimental results and the observed incidence of amino acid residues in the i + 1 and i + 2 positions in β‐turns, to determine the features of VCD spectra of type I and II β‐turns. The results were correlated with electronic circular dichroism (ECD) spectra and VCD spectra calculated from conformational data obtained by molecular dynamics (MD) simulations. All cyclic tetrapeptides yielded VCD signals with a higher frequency negative and a lower frequency positive couplet with negative lobes overlapping. MD simulations confirmed the conformational homogeneity of these peptides in solution. Comparison with ECD spectroscopy, MD, and quantum chemical calculation results suggested that the low frequency component of VCD spectra originating from the tertiary amide vibrations could be used to distinguish between types of β‐turn structures. On the basis of this observation, VCD spectroscopic features of type II and VIII β‐turns and ECD spectroscopic properties of a type VIII β‐turn were suggested. The need for independent experimental as well as theoretical investigations to obtain decisive conformational information was recognized. © 2006 Wiley Periodicals, Inc. Biopolymers 85: 1–11, 2007.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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“…Most attempts to identify such relationships have proceeded by identifying a common structural motif, then characterizing the frequencies of occurrence of each amino acid at each position in the motif (Aurora et al, 1994;Chan et al, 1993;E®mov, 1993;Hutchinson & Thornton, 1994;Jime Ânez et al, 1994;Unger & Sussman, 1993;Zhu & Blundell, 1996). In particular, sequence patterns for tight turns (Hutchinson & Thornton, 1994;Yang et al, 1996) and helix caps (Aurora et al, 1994;Donnelly et al, 1994;elMasry & Fersht, 1994;Jime Ânez et al, 1994; have been described. More comprehensive approaches have clustered structural segments into classes using measures of structural similarity, and then tabulated sequence preferences for each of the classes (Oliva et al, 1997;Rooman et al, 1990;Unger et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Prediction of local structure in proteins using a library of sequence-structure motifs

Bystroff

Baker

1998

Journal of Molecular Biology

310

267

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We describe a new method for local protein structure prediction based on a library of short sequence pattern that correlate strongly with protein three-dimensional structural elements. The library was generated using an automated method for ®nding correlations between protein sequence and local structure, and contains most previously described local sequence-structure correlations as well as new relationships, including a diverging type-II b-turn, a frayed helix, and a proline-terminated helix. The query sequence is scanned for segments 7 to 19 residues in length that strongly match one of the 82 patterns in the library. Matching segments are assigned the three-dimensional structure characteristic of the corresponding sequence pattern, and backbone torsion angles for the entire query sequence are then predicted by piecing together mutually compatible segment predictions. In predictions of local structure in a test set of 55 proteins, about 50% of all residues, and 76% of residues covered by high-con®dence predictions, were found in eight-residue segments within 1.4 A Ê of their true structures. The predictions are complementary to traditional secondary structure predictions because they are considerably more speci®c in turn regions, and may contribute to ab initio tertiary structure prediction and fold recognition.

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Free Energy Determinants of Secondary Structure Formation: III. β-Turns and their Role in Protein Folding

Cited by 108 publications

References 36 publications

Free energy determinants of tertiary structure and the evaluation of protein models

Free energy determinants of tertiary structure and the evaluation of protein models

Optical spectroscopic elucidation of β‐turns in disulfide bridged cyclic tetrapeptides

Prediction of local structure in proteins using a library of sequence-structure motifs

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