Analysis of the relationship between side-chain conformation and secondary structure in globular proteins

McGregor, Malcolm J.; Islam, Suhail A.; Sternberg, Michael J.E.

doi:10.1016/0022-2836(87)90314-7

Cited by 404 publications

(223 citation statements)

References 16 publications

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“…This is not unexpected because ROC is given the actual backbone structure of the wild-type protein. The major discrepancy in prediction involves a rotamer change of Leu133 from the most statistically favorable leucine rotamer to the second most favorable (McGregor et al, 1987). For variant II, SoftROC gives the more accurate prediction, as shown in Figure 7(c) and (d).…”

Section: T4 Lysozyme Hydrophobic Core Variantsmentioning

confidence: 95%

“…For variant II, SoftROC gives the more accurate prediction, as shown in Figure 7(c) and (d). The difference in prediction involves a major change in the orientation of tryptophan 153 and a correlated change of Leu129 into a statistically unfavorable rotamer in the ROC model (McGregor et al, 1987). In this case, the incorrect predictions are presumably due to the inability of ROC to accommodate the large tryptophan residue in the context of the wild-type backbone structure.…”

Section: T4 Lysozyme Hydrophobic Core Variantsmentioning

confidence: 99%

See 1 more Smart Citation

Side-chain and backbone flexibility in protein core design 1 1Edited by A. R. Fersht

Desjarlais

Handel

1999

Journal of Molecular Biology

135

105

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We have developed a computational approach for the design and prediction of hydrophobic cores that includes explicit backbone¯exibility. The program consists of a two-stage combination of a genetic algorithm and monte carlo sampling using a torsional model of the protein. Backbone structures are evaluated either by a canonical force-®eld or a constraining potential that emphasizes the preservation of local geometry. The utility of the method for protein design and engineering is explored by designing three novel hydrophobic core variants of the protein 434 cro. We use the new method to evaluate these and previously designed 434 cro variants, as well as a series of phage T4 lysozyme variants. In order to properly evaluate the in¯uence of backbone¯exibility, we have also analyzed the effects of varying amounts of side-chain¯exibility on the performance of ®xed backbone methods. Comparison of results using a ®xed versus¯exible backbone reveals that, surprisingly, the two methods are almost equivalent in their abilities to predict relative experimental stabilities, but only when full side-chain¯exibility is allowed. The prediction of core side-chain structure can vary dramatically between methods. In some, but not all, cases the¯exible backbone method is a better predictor of structure. The development of a¯exible backbone approach to core design is particularly important for attempts at de novo protein design, where there is no prior knowledge of a precise backbone structure.

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Section: T4 Lysozyme Hydrophobic Core Variantsmentioning

confidence: 95%

Section: T4 Lysozyme Hydrophobic Core Variantsmentioning

confidence: 99%

Side-chain and backbone flexibility in protein core design 1 1Edited by A. R. Fersht

Desjarlais

Handel

1999

Journal of Molecular Biology

135

105

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“…The five MI1 helices were placed in the regular conical disposition detailed in [lo] with the homologous residues at the same level, their N-terminal being on the cytoplasmic side. Assuming the CIY atoms of the labelled serines to face the center of the pore, the 'helix wheels ' request [8] that the Ccu situated on the interior wall are those of residues 1,4,8,12,15,19 (in the simplified notation of fig.1). According to our previous discussion [&lo], the upper'limits of the MIIs are set 4 residues below Pro 265 in LY and homologs in p, y, 6.…”

Section: Methodsmentioning

confidence: 99%

Energy profiles in the acetylcholine receptor (AChR) channel The MII‐helix model and the role of the remaining helices

Furois-Corbin¹,

Pullman²

1989

FEBS Letters

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It is demonstrated by theoretical computations that no favorable energy profile for cation transfer can be obtained in a model of the AChR channel constructed with the sole five MI1 helices of the inner wall. A favorable profile is obtained upon including the effect of the remaining helices of the five subunits. The decisive role, for the exit of the ion, of the charged residues situated at the N-terminal of the MI1 segments, established before, is underlined further. The role of the other elements of the channel wall (peptide carbonyl oxygens, hydrocarbon residues and polar side chains) is analyzed.Acetylcholine receptor channel; MII-helix model; Helix dipole, a-; Subunit dipole; Na+ energy profile

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“…The energetically favorable rotamer (g − (−60°; +90°)) of Trp87 and the residues in the flanking β-strands are shown in Figure 9. Analysis of the distribution of Trp rotamers in globular proteins show that the rotamer g − is the most favorable [37,38] in β-strands, particularly at the center of β-strands [38]. It is interesting to note that the estimated contribution of the tryptophan side chain (B b rotational strength) in the g − (−60°; +90°) conformation to the far-UV CD is −0.39 DBM (Debye-Bohr magneton, 1 DBM= 0.9273 × 10 −38 cgs units) [28], which corroborates the far-UV CD data for the TL mutants.…”

Section: Resolution Of the Near-uv CD Spectra Of Y87w The "Dmso-likementioning

confidence: 99%

Site-directed circular dichroism of proteins: 1Lb bands of Trp resolve position-specific features in tear lipocalin

Gasymov

Abduragimov

Glasgow

2008

Analytical Biochemistry

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The absorption spectra of N-acetyl-L-tryptophanamide in various solvents were resolved into the sums of the 1 L a and 1 L b components. The relative intensities of the 0-0 transitions of the 1 L b bands correlate linearly with the solvent polarity values . A novel strategy, which utilizes a set of the experimental 1 L b bands, was employed to resolve the near-UV CD spectra of tryptophanyl residues. Resolved spectral parameters from the single-tryptophan mutants of tear lipocalin (TL), F99W and Y87W, corroborate the fluorescence as well as structural data of TL. Analysis of the 1 L b bands of the Trp CD spectra in proteins is a valuable tool to obtain the local features. The "DMSOlike" 1 L b band of Trp CD spectra may be used as a "fingerprint" to identify the tryptophanyl side chains in situations where the benzene rings of Trp have van der Waals interactions with the side chains of its nearest neighbor. In addition, the signs and intensities of the components hold information about the side-chain conformations and dynamics in proteins. Combined with Trp mutagenesis, this method we call site-directed circular dichroism is broadly applicable to various proteins to obtain the position-specific data.

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Analysis of the relationship between side-chain conformation and secondary structure in globular proteins

Cited by 404 publications

References 16 publications

Side-chain and backbone flexibility in protein core design 1 1Edited by A. R. Fersht

Side-chain and backbone flexibility in protein core design 1 1Edited by A. R. Fersht

Energy profiles in the acetylcholine receptor (AChR) channel The MII‐helix model and the role of the remaining helices

Site-directed circular dichroism of proteins: 1Lb bands of Trp resolve position-specific features in tear lipocalin

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