Determination of Free Energies of N-Capping in .alpha.-Helixes by Modification of the Lifson-Roig Helix-Coil Theory To Include N- and C-Capping

Doig, Andrew J.; Chakrabartty, Avijit; Klingler, Tod M.; Baldwin, Robert L.

doi:10.1021/bi00177a033

Cited by 179 publications

(264 citation statements)

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“…Peptide sequences are designed to be approximately 50% helical, where ellipticity is most sensitive to small changes in side chain interaction energy. We analyze the data using a further modified form of the Lifson-Roig helix-coil theory (Doig et al, 1994) that includes terms for i, i + 3 and i, i + 4 side chain interactions.…”

Section: Ac-ygaakaaaakaaaakaa-nhmentioning

confidence: 99%

“…The original Lifson-Roig model has been previously modified to include N-and C-capping by defining new statistical weights for the coil residues adjacent to helical neighbors (Doig et al, 1994). Residues in the c state with an h state C-terminal neighbor are assigned weight n, and those with an N-terminal helical neighbor are assigned weight c. Residues in the c state that have both an N-terminal and C-terminal h state neighbor are assigned the geometric mean of the two capping weights, p and q are thus equilibrium constants for formation of an interaction in an a-helix.…”

Section: Theorymentioning

confidence: 99%

“…Even whenp is very large, helix formation is not complete because fraying still occurs outside the region of the favorably interacting residues. The peptide with an interaction near the helix terminus reaches a higher helix content than that with an interaction near the peptide center because fraying occurs more When all the interaction parameters are set equal to unity, this partition function is equivalent to that determined from the model of Doig et al (1994). Many properties of the system can be calculated from the partition function, including the average number of residues in helical conformation, the average number of helical hydrogen bonds, and the probability of an individual residue being in a given conformation.…”

Section: Theorymentioning

confidence: 99%

“…The behavior of such molecules indicates that helix stability is a function of the intrinsic helix-forming tendencies of constituent amino acids ; reviewed by Scholtz et al, 1991;, capping preferences at the carboxyl and amino termini (Presta & Rose, 1988;Richardson & Richardson, 1988;Serrano & Fersht, 1989;Lyu et al, 1992;Forood et al, 1993;Doig et al, 1994;Doig & Baldwin, 1995), and specific side chain-side chain interactions. These side chain interactions include salt bridges (Marqusee & Baldwin, 1987;Lyuetal., 1989;Andersonetal., 1990;Fairmanetal., 1990;Horovitz et al, 1990;Cans et al, 1991;Stellwagen et al, 1992;HuyghuesDespointes et al, 1993;Scholtz et al, 1993), hydrogen bonds Huyghues-Despointes et al, 1995), and hydrophobic interactions Armstrong et al, 1993;Padmanabhan & Baldwin, 1994a, 1994bViguera & Serrano, 1995).…”

mentioning

confidence: 99%

“…These side chain interactions include salt bridges (Marqusee & Baldwin, 1987;Lyuetal., 1989;Andersonetal., 1990;Fairmanetal., 1990;Horovitz et al, 1990;Cans et al, 1991;Stellwagen et al, 1992;HuyghuesDespointes et al, 1993;Scholtz et al, 1993), hydrogen bonds Huyghues-Despointes et al, 1995), and hydrophobic interactions Armstrong et al, 1993;Padmanabhan & Baldwin, 1994a, 1994bViguera & Serrano, 1995). Charged residues may also interact with the helix-dipole (Hol et al, 1978;Armstrong et al, 1993;HuyghuesDespointes et al, 1993;Scholtz et al, 1993), but these energies are partly subsumed into capping preferences (Doig et al, 1994).…”

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Addition of side chain interactions to modified Lifson‐Roig helix‐coil theory: Application to energetics of Phenylalanine‐Methionine interactions

1995

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We introduce here i, i + 3 and i, i + 4 side chain interactions into the modified Lifson-Roig helix-coil theory of Doig et al. (1994, Biochemistry 33:3396-3403). The helixkoil equilibrium is a function of initiation, propagation, capping, and side chain interaction parameters. If each of these parameters is known, the helix content of any isolated peptide can be predicted. The model considers every possible conformation of a peptide, is not limited to peptides with only a single helical segment, and has physically meaningful parameters. We apply the theory to measure the i, i + 4 interaction energies between Phe and Met side chains. Peptides with these residues spaced i, i + 4 are significantly more helical than controls where they are spaced i, i + 5 . Application of the model yields A G for the Phe-Met orientation to be -0.75 kcal.mol", whereas that for the Met-Phe orientation is -0.54 kcal.mol-'. These orientational preferences can be explained, in part, by rotamer preferences for the interacting side chains. We place Phe-Met i , i + 4 at the N-terminus, the C-terminus, and in the center of the host peptide. The model quantitatively predicts the observed helix contents using a single parameter for the side chain-side chain interaction energy. This result indicates that the model works well even when the interaction is at different locations in the helix.

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Section: Ac-ygaakaaaakaaaakaa-nhmentioning

confidence: 99%

Section: Theorymentioning

confidence: 99%

Section: Theorymentioning

confidence: 99%

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Addition of side chain interactions to modified Lifson‐Roig helix‐coil theory: Application to energetics of Phenylalanine‐Methionine interactions

1995

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Molten globule state of equine β-Lactoglobulin

Ikeguchi¹,

Kato²,

Shimizu³

et al. 1997

Proteins

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The acid-unfolded state of equine beta-lactoglobulin was characterized by means of circular dichroism, nuclear magnetic resonance, analytical gel-filtration chromatography, and analytical centrifugation. The acid-unfolded state of equine beta-lactoglobulin has a substantial secondary structure as shown by the far-ultraviolet circular dichroism spectrum but lacks persistent tertiary packing of the side chains as indicated by the near-ultraviolet circular dichroism and nuclear magnetic resonance spectra. It is nearly as compact as the native conformation as shown by the gel filtration and sedimentation experiments, and it has the exposed hydrophobic surface as indicated by its tendency to aggregate. All of these characteristics indicate that the acid-unfolded state of equine beta-lactoglobulin is a molten globule state. The alpha helix content in the acid-unfolded state, which has been estimated from the circular dichroism spectrum, is larger than that in the native state, suggesting the presence of nonnative alpha helices in the molten globule state. This result suggests the generality of the intermediate with nonnative alpha helices during the folding of proteins having the beta-clam fold.

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Predicting helical segments in proteins by a helix-coil transition theory with parameters derived from a structural database of proteins

Misra

Wong

1997

Proteins

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A novel helix-coil transition theory has been developed. This new theory contains more types of interactions than similar theories developed earlier. The parameters of the models were obtained from a database of 351 nonhomologous proteins. No manual adjustment of the parameters was performed. The interaction parameters obtained in this manner were found to be physically meaningful, consistent with current understanding of helix stabilizing/destabilizing interactions. Novel insights into helix stabilizing/destabilizing interactions have also emerged from this analysis. The theory developed here worked well in sorting out helical residues from amino acid sequences. If the theory was forced to make prediction on every residue of a given amino acid sequence, its performance was the best among ten other secondary structural prediction algorithms in distinguishing helical residues from nonhelical ones. The theory worked even better if one only required it to make prediction on residues that were "predictable" (identifiable by the theory); > 90% predictive reliability could be achieved. The helical residues or segments identified by the helix-coil transition theory can be used as secondary structural contraints to speed up the prediction of the three-dimensional structure of a protein by reducing the dimension of a computational protein folding problem. Possible further improvements of this helix-coil transition theory are also discussed.

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Determination of Free Energies of N-Capping in .alpha.-Helixes by Modification of the Lifson-Roig Helix-Coil Theory To Include N- and C-Capping

Cited by 179 publications

References 27 publications

Addition of side chain interactions to modified Lifson‐Roig helix‐coil theory: Application to energetics of Phenylalanine‐Methionine interactions

Addition of side chain interactions to modified Lifson‐Roig helix‐coil theory: Application to energetics of Phenylalanine‐Methionine interactions

Molten globule state of equine β-Lactoglobulin

Predicting helical segments in proteins by a helix-coil transition theory with parameters derived from a structural database of proteins

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