Hydrophobicity scales and computational techniques for detecting amphipathic structures in proteins

Cornette, James L.; Cease, Kemp B.; Margalit, Hanah; Spouge, John L.; Berzofsky, Jay A.; DeLisi, Charles

doi:10.1016/0022-2836(87)90189-6

Cited by 611 publications

(454 citation statements)

References 47 publications

Supporting

Mentioning

439

Contrasting

Order By: Relevance

“…The most polar amino acid is aspartic acid with ⌬Gapp ϭ 3.49 kcal/mol [48]. Several other amino acid hydrophobicity scales-such as Cornette [35], Kyte-Doolitle [49], transmembrane tendency scale [50]-differ slightly from the Hessa scale. Analysis of the major hydrophobicity scales confirms their applicability to describe a general trend of periodic distribution of hydrophobic and hydrophilic amino acids in amphipathic peptides and proteins.…”

Section: Ecd Pia Analysismentioning

confidence: 99%

“…ECD FT-ICR MS of six doubly protonated horse myoglobin tryptic fragments ( [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16], [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31], [32][33][34][35][36][37][38][39][40][41][42] Figure S2) and with vibrational activation ( Figure 5) confirm preferential and sometimes periodic product ion formation from peptides with mainly ␣-helical or ␤-turn secondary structure in solution (before protein digestion). Predominantly z-ions are observed because of preferential charge retention at the C-terminal Lys or Arg basic residue upon electron capture, as expected for doubly charged tryptic peptides.…”

Section: Ecd Of Doubly Charged Amphipathic Peptidesmentioning

confidence: 99%

“…In general, amino acids have strong positiondependent probabilities of appearance in ␣-helical or ␤-strand peptides and proteins [34]. Amphipathic peptides are those that exhibit a periodic (typically every 3 to 4 residues) distribution of hydrophobic and hydrophilic amino acids along the peptide backbone [35]. The characteristic amino acid distribution in amphipathic peptides results in formation of two opposite faces: hydrophobic and hydrophilic.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Periodic sequence distribution of product ion abundances in electron capture dissociation of amphipathic peptides and proteins

Hamidane

Tsybin

et al. 2009

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

The rules for product ion formation in electron capture dissociation (ECD) mass spectrometry of peptides and proteins remain unclear. Random backbone cleavage probability and the nonspecific nature of ECD toward amino acid sequence have been reported, contrary to preferential channels of fragmentation in slow heating-based tandem mass spectrometry. Here we demonstrate that for amphipathic peptides and proteins, modulation of ECD product ion abundance (PIA) along the sequence is pronounced. Moreover, because of the specific primary (and presumably secondary) structure of amphipathic peptides, PIA in ECD demonstrates a clear and reproducible periodic sequence distribution. On the one hand, the period of ECD PIA corresponds to periodic distribution of spatially separated hydrophobic and hydrophilic domains within the peptide primary sequence. On the other hand, the same period correlates with secondary structure units, such as ␣-helical turns, known for solution-phase structure. Based on a number of examples, we formulate a set of characteristic features for ECD of amphipathic peptides and proteins: (1) periodic distribution of PIA is observed and is reproducible in a wide range of ECD parameters and on different experimental platforms; (2) local maxima of PIA are not necessarily located near the charged site; (3) ion activation before ECD not only extends product ion sequence coverage but also preserves ion yield modulation; (4) the most efficient cleavage (e.g. global maximum of ECD PIA distribution) can be remote from the charged site; (5) the number and location of PIA maxima correlate with amino acid hydrophobicity maxima generally to within a single amino acid displacement; and (6) preferential cleavage sites follow a selected hydrogen spine in an ␣-helical peptide segment. Presently proposed novel insights into ECD behavior are important for advancing understanding of the ECD mechanism, particularly the role of peptide sequence on PIA. An improved ECD model could facilitate protein sequencing and improve identification of unknown proteins in proteomics technologies. In structural biology, the periodic/preferential product ion yield in ECD of ␣-helical structures potentially opens the way toward de novo site-specific secondary structure determination of peptides and proteins in the gas phase and its correlation with solution-phase structure. (J Am Soc Mass Spectrom 2009, 20, 1182-1192) © 2009 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry B iomolecular fragmentation in the gas phase by electron capture dissociation (ECD) [1-3] and electron-transfer dissociation (ETD) [4,5] is particularly attractive for mass spectrometry (MS)-based peptide and protein structural analysis. In ECD/ETD, interaction of a multiply charged peptide or protein ion with an electron/anion results in cleavage of NOC ␣ bonds along the peptide backbone, including chargesite-remote backbone cleavages [2]. ECD is useful for peptide sequence tag generation on a chromatographic timescale for protein identificat...

show abstract

Section: Ecd Pia Analysismentioning

confidence: 99%

Section: Ecd Of Doubly Charged Amphipathic Peptidesmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Periodic sequence distribution of product ion abundances in electron capture dissociation of amphipathic peptides and proteins

Hamidane

Tsybin

et al. 2009

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

show abstract

“…Note, however, that the number of data points for Phe and Met is very limited. Note also that we have, for illustrative purposes, used the scale of FauchCre & PliSka (l983), but different solvent transfer and hydrophobicity scales show substantial variation among themselves (Cornette et al, 1987). Another major concern is the reliability of the cavity calculations, especially when the volumes are relatively small (see below).…”

Section: The Energetics Of Cavity Formationmentioning

confidence: 99%

The response of T4 lysozyme to large‐to‐small substitutions within the core and its relation to the hydrophobic effect

et al. 1998

View full text Add to dashboard Cite

To further examine the structural and thermodynamic basis of hydrophobic stabilization in proteins, all of the bulky non-polar residues that are buried or largely buried within the core of T4 lysozyme were substituted with alanine. In 25 cases, including eight reported previously, it was possible to determine the crystal structures of the variants. The structures of four variants with double substitutions were also determined. In the majority of cases the "large-to-small" substitutions lead to internal cavities. In other cases declivities or channels open to the surface were formed. In some cases the structural changes were minimal (mainchain shifts 5 0.3 A); in other cases mainchain atoms moved up to 2 A.In the case of Ile 29 -+ Ala the structure col!apsed to such a degree that the volume of the putative cavity was zero. Crystallographic analysis suggests that the occupancy of the engineered cavities by solvent is usually low. The mutants Val 149 4 Ala (V149A) and Met 6 -+ Ala (M6A), however, are exceptions and have, respectively, one and two well-ordered water molecules within the. cavity. The Val 149 -+ Ala substitution allows the solvent molecule to hydrogen bond to polar atoms that are occluded in the wild-type molecule. Similarly, the replacement of Met 6 with alanine allows the two solvent molecules to hydrogen bond to each other and to polar atoms on the protein. Except for Val 149 -+ Ala the loss of stability of all the cavity mutants can be rationalized as a combination of two terms. The first is a constant for a given class of substitution (e.g., -2.1 kcal/mol for all Leu + Ala substitutions) and can be considered as the difference between the free energy of transfer of leucine and alanine from solvent to the core of the protein. The second term can be considered as the energy cost of forming the cavity and is consistent with a numerical value of 22 cal mol" k 3 . Physically, this term is due to the loss of van der Waal's interactions between the bulky sidechain that is removed and the atoms that form the wall of the cavity. The overall results are consistent with the prior rationalization of Leu + Ala mutants in T4 lysozyme by Eriksson et al. (Eriksson et al., 1992, Science 255:178-183).

show abstract

“…The proprietary techniques used to analyze and target GAL's leading hydrophobic sequence autocovariance matrix eigenmodes include: (1) numerical transformation of the GAL sequence into amino acid solvent partition-derived hydrophobicities in kcal/mol [49][50][51][52] ;(2) linear decomposition of hydrophobically transformed GAL sequence's lagged autocovariance matrix, generating leading eigenvalues, eigenvectors, and eigenfunctions. The latter are formed by composition of the eigenvectors with the sequentially averaged hydrophobic series 1,53,54 ; (3) all poles, maximum entropy, power spectral transformation of the leading eigenfunctions to partially describe and index the wavelengths of the leading hydrophobic eigenmodes 1,[55][56][57] ; (4) wavelet transformation of the leading eigenfunctions to obtain an independent approximation of the wavelengths of the leading mode densities that were indicated by their power (frequency) spectral transformations, and to suggest the sequence location(s) of their leading eigenmode densities 7,11,12,[58][59][60][61][62][63] ; (5) weighted random assignment of amino acids by hydrophobic group to the partitioned compound eigenvector template, derived from, (2) generating the hydrophobic mode matched, candidate peptide ligands.…”

Section: The Results Of Gal Analyses and Peptide-ligand Design Elucidmentioning

confidence: 99%

Designing allosteric peptide ligands targeting a globular protein

et al. 2006

View full text Add to dashboard Cite

Patented signal analytic algorithms applied to hydrophobically transformed, numerical amino acid sequences have previously been used to design short, protein‐targeted, L or D retro‐inverso peptides. These peptides have demonstrated allosteric and/or indirect agonist effects on a variety of G‐protein and tyrosine kinase coupled membrane receptors with 30% to over 80% hit rates. Here we extend these approaches to a globular protein target. We designed eight peptide ligands targeting an ELISA antibody responsive protein, β‐galactosidase, βGAL. Three of the eight 14mer peptides allosterically activated βGAL with ELISA methodology. Using Bayesian statistics, this 38% hit rate would have occurred 2 × 10−9 by chance. These peptides demonstrated binding site competitive or noncompetitive interactions, suggesting allosteric site multiplicity with respect to their βGAL binding‐mediated ELISA signal. Kinetic studies demonstrated the temperature dependence of the βGAL peptide binding functions. Using the van't Hoff relation, we found evidence for enthalpy–entropy compensation. This relation is often found for hydrophobic interactions in aqueous media, and is consistent with the postulated hydrophobic series encoding underlying our protein‐targeted, peptide design methods. It appears that our algorithmic, hydrophobic autocovariance eigenvector template approach to the design of allosteric peptides targeting membrane receptors may also be applicable to the design of peptide ligands targeting nonmembrane involved globular proteins. © 2006 Wiley Periodicals, Inc. Biopolymers 85: 38–59, 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

show abstract

Hydrophobicity scales and computational techniques for detecting amphipathic structures in proteins

Cited by 611 publications

References 47 publications

Periodic sequence distribution of product ion abundances in electron capture dissociation of amphipathic peptides and proteins

Periodic sequence distribution of product ion abundances in electron capture dissociation of amphipathic peptides and proteins

The response of T4 lysozyme to large‐to‐small substitutions within the core and its relation to the hydrophobic effect

Designing allosteric peptide ligands targeting a globular protein

Contact Info

Product

Resources

About