Helix geometry in proteins

Barlow, D. J.; Thornton, Janet M.

doi:10.1016/0022-2836(88)90641-9

Cited by 1,032 publications

(863 citation statements)

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“…Here, however, not all alanines are equivalent. Some are solvent- a If the calculation is repeated with an "average" a-helix (4 = -62", $ = -41") (Barlow & Thornton, 1988), the individual discrepancies increase by about 0.04 A, but the overall trend is the same.…”

Section: Structure Of the Polyalanine Helixmentioning

confidence: 99%

Multiple alanine replacements within α‐helix 126–134 of T4 lysozyme have independent, additive effects on both structure and stability

1992

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In a systematic attempt to identify residues important in the folding and stability of T4 lysozyme, five amino acids within a-helix 126-134 were substituted by alanine, either singly or in selected combinations. Together with three alanines already present in the wild-type structure this provided a set of mutant proteins with up to eight alanines in sequence. All the variants behaved normally, suggesting that the majority of residues in the a-helix are nonessential for the folding of T4 lysozyme. Of the five individual alanine substitutions it is inferred that four result in slightly increased protein stability and one, the replacement of a buried leucine with alanine, substantially decreased stability. The results support the idea that alanine is a residue of high helix propensity. The change in protein stability observed for each of the multiple mutants is approximately equal to the sum of the energies associated with each of the constituent substitutions.All of the variants could be crystallized isomorphously with wild-type lysozyme, and, with one trivial exception, their structures were determined at high resolution. Substitution of the largely solvent-exposed residues Asp 127, Glu 128, and Val 131 with alanine caused essentially no change in structure except at the immediate site of replacement. Substitutions of the partially buried Asn 132 and the buried Leu 133 with alanine were associated with modest ( 5 0 . 4 A) structural adjustments. The structural changes seen in the multiple mutants were essentially a combination of those seen in the constituent single replacements. The different replacements therefore act essentially independently not only so far as changes in energy are concerned but also in their effect on structure. The destabilizing replacement Leu 133 +Ala made a-helix 126-134 somewhat less regular. Incorporation of additional alanine replacements tended to make the helix more uniform. For the penta-alanine variant a distinct change occurred in a crystal-packing contact, and the "hinge-bending angle" between the amino-and carboxyterminal domains changed by 3.6". This tends to confirm that such hinge-bending in T4 lysozyme is a low-energy conformational change.Keywords: alanine; lysozyme; protein folding; protein structure; thermostability In a systematic attempt to identify residues important in the folding and stability of phage T4 lysozyme we previously substituted four alanines within the a-helix that includes residues 126-134 . The helix is amphipathic, located on the surface of the carboxy-terminal domain, and is remote from the active site ( Fig. 1; Kinemage 1). In wild-type lysozyme this a-helix already includes three alanines. It was found that substitution of three solvent-exposed residues, Glu 128, Val 131, and Asn

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Section: Structure Of the Polyalanine Helixmentioning

confidence: 99%

Multiple alanine replacements within α‐helix 126–134 of T4 lysozyme have independent, additive effects on both structure and stability

1992

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“…The analysis of the subclasses reveals five important helix subclasses-(i)right handed regular α -helix [1,3], (ii) extended helix, (iii) c-cap helix, (iv) kinked helix [3], and (v) curved helix [2]. We find that the regular α -helix is the most dominant subclass having as much as 76% mixing proportion.…”

Section: Resultsmentioning

confidence: 99%

“…The right handed α -helices are found more frequently in the proteins than their left handed counterparts [1]. The right handed α -helix is a regular structure with backbone torsion angles of φ = –63 and ψ = –43 [1-3]. …”

Section: Introductionmentioning

confidence: 99%

“…For example, proline residue beyond first turn in α -helix causes a kink in its structure [3]. The perturbations in the helix geometry give rise to different subclasses of α -helix.…”

Section: Introductionmentioning

confidence: 99%

“…The perturbations in the helix geometry give rise to different subclasses of α -helix. The three types of helix subclasses are reported in the literature: linear, curved and kinked [2,3]. It is well known that the structural variations in α -helix are encoded in its sequence.…”

Section: Introductionmentioning

confidence: 99%

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Characterization and sequence prediction of structural variations in α-helix

Tendulkar

Wangikar

2011

BMC Bioinformatics

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BackgroundThe structure conservation in various α-helix subclasses reveals the sequence and context dependent factors causing distortions in the α-helix. The sequence-structure relationship in these subclasses can be used to predict structural variations in α-helix purely based on its sequence. We train support vector machine(SVM) with dot product kernel function to discriminate between regular α-helix and non-regular α-helices purely based on the sequences, which are represented with various overall and position specific propensities of amino acids.ResultsWe characterize the structural distortions in five α-helix subclasses. The sequence structure correlation in the subclasses reveals that the increased propensity of proline, histidine, serine, aspartic acid and aromatic amino acids are responsible for the distortions in regular α-helix. The N-terminus of regular α-helix prefers neutral and acidic polar amino acids, while the C-terminus prefers basic polar amino acid. Proline is preferred in the first turn of regular α-helix , while it is preferred to produce kinked and curved subclasses. The SVM discriminates between regular α-helix and the rest with precision of 80.97% and recall of 88.05%.ConclusionsThe correlation between structural variation in helices and their sequences is manifested by the performance of SVM based on sequence features. The results presented here are useful for computational design of helices. The results are also useful for prediction of structural perturbations in helix sequence purely based on its sequence.

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United-residue force field for off-lattice protein-structure simulations: III. Origin of backbone hydrogen-bonding cooperativity in united-residue potentials

Liwo¹,

Kaźmierkiewicz²,

Czaplewski³

et al. 1998

J. Comput. Chem.

164

312

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Based on the dipole model of peptide groups developed in our earlier work [Liwo et al., Prot. Sci., 2, 1697 (1993)], a cumulant expansion of the average free energy of the system of freely rotating peptide‐group dipoles tethered to a fixed α‐carbon trace is derived. A graphical approach is presented to find all nonvanishing terms in the cumulants. In particular, analytical expressions for three‐ and four‐body (correlation) terms in the averaged interaction potential of united peptide groups are derived. These expressions are similar to the cooperative forces in hydrogen bonding introduced by Koliński and Skolnick [J. Chem. Phys., 97, 9412 (1992)]. The cooperativity arises here naturally from the higher order terms in the power‐series expansion (in the inverse of the temperature) for the average energy. Test calculations have shown that addition of the derived four‐body term to the statistical united‐residue potential of our earlier work [Liwo et al., J. Comput. Chem., 18, 849, 874 (1997)] greatly improves its performance in folding poly‐l‐alanine into an α‐helix. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 259–276, 1998

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Helix geometry in proteins

Cited by 1,032 publications

References 35 publications

Multiple alanine replacements within α‐helix 126–134 of T4 lysozyme have independent, additive effects on both structure and stability

Multiple alanine replacements within α‐helix 126–134 of T4 lysozyme have independent, additive effects on both structure and stability

Characterization and sequence prediction of structural variations in α-helix

United-residue force field for off-lattice protein-structure simulations: III. Origin of backbone hydrogen-bonding cooperativity in united-residue potentials

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