Wavelet transforms for the characterization and detection of repeating motifs

Murray, Kevin B.; Gorse, Denise; Thornton, Janet M.

doi:10.1006/jmbi.2001.5332

Cited by 92 publications

(69 citation statements)

References 45 publications

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“…Inspection of features at a specified length scale along the sequence would, of course, involve different k values in sequences of different length.) In this respect it differs from Fourier methods and other periodicity-based approaches previously proposed by a number of workers (12)(13)(14)(15)(16)(17)(18), who have used these tools to examine the role of sequence in local structure formation and particularly in studying the role of hydrophobicity in protein sequences. Recent studies (19) have used simple potentials to relate sequence and secondary structure prediction in model proteins.…”

Section: Modelmentioning

confidence: 99%

Global characteristics of protein sequences and their implications

Rackovsky

2010

Proc. Natl. Acad. Sci. U.S.A.

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Computational studies of the relationships between protein sequence, structure, and folding have traditionally relied on purely local sequence representations. Here we show that global representations, on the basis of parameters that encode information about complete sequences, contain otherwise inaccessible information about the organization of sequences. By studying the spectral properties of these parameters, we demonstrate that amino acid physical properties fall into two distinct classes. One class is comprised of properties that favor sequentially localized interaction clusters. The other class is comprised of properties that favor globally distributed interactions. This observation provides a bridge between two classic models of protein folding-the collapse model and the nucleation model-and provides a basis for understanding how any degree of intermediacy between these two extremes can occur.proteomics | sequence analysis B ioinformatic studies of protein sequences have concentrated almost exclusively on their local properties. The relationship between local sequence properties and local folding has been extensively examined. Sequence homology studies have concentrated on developing methods for establishing local equivalences between corresponding residues in pairs of sequences. It has become increasingly clear, however, that a purely local view of protein sequences is not adequate. In a number of recent studies (1-6), we have demonstrated quantitatively that there are intrinsic limitations to the informatic power of local descriptions of protein sequence, particularly with respect to the encoding of structural information. It is clear, however, that sequence does completely determine protein structure, and it therefore follows that folding instructions must be encrypted in global, rather than local, sequence information. In the present work, we discuss some fundamental global properties of protein sequences and examine their implications for mechanisms of protein folding. ModelA necessary preliminary to any meaningful discussion of sequence characteristics is the conversion of protein sequences into a numerical form amenable to systematic analysis. We follow a procedure set forth in previous work (7-9), by using the 10 Kidera property factors (10, 11) , which form an orthonormal and essentially complete basis set for the known physical properties of the amino acids, to represent an amino acid as a 10-vector. (The Kidera factors are given in Table 1.) A complete protein sequence is then represented by a set of 10 N-member numerical strings, each of which records the course of one property factor along the N-residue sequence. These strings can be Fourier transformed, leading to a representation of the sequence by a set of sine and cosine Fourier coefficients. Each of these coefficients, which is labeled by a wave number k and a property identifier l, encodes information about the entire sequence of the protein. Furthermore, the Fourier components are determined by information associated with different int...

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Section: Modelmentioning

confidence: 99%

Global characteristics of protein sequences and their implications

Rackovsky

2010

Proc. Natl. Acad. Sci. U.S.A.

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“…This naturally led to our applications of some of these and related techniques (Broomhead et al, 1987;Broomhead and King, 1986;Ott et al, 1994) to hydrophobically transformed amino-acid sequences and/or subsequences (Manavalen and Ponnuswamy, 1978;Nozaki and Tanford, 1971;Reynolds et al, 1974;Zimmerman et al, 1968), including those that are conformationally disordered in globular proteins (Mandell et al, 1997a(Mandell et al, , b, 1998b, polyproteins (Mandell et al, 1998c), membrane channels and transporters, (Mandell et al, 1998a;Selz et al, 1998) and Type I (Mandell et al, 2001) and Gprotein-coupled (Mandell et al, 1997c(Mandell et al, , 2000b) membrane receptors. Recently, other groups have begun applying some of these techniques of one-dimensional signal analysis to protein structural characterization and prediction (Hirakawa et al, 1999;Murray et al, 2002;Lio and Vannucci, 2000;Giuliani et al, 2002;Wouters et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Cellular and Behavioral Effects of D2 Dopamine Receptor Hydrophobic Eigenmode-Targeted Peptide Ligands

Mandell

Selz

Owens

et al. 2003

Neuropsychopharmacol

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Patterns in G-protein-coupled receptors' hydrophobically transformed amino-acid sequences can be computationally characterized as hierarchies of autocorrelation waves, 'hydrophobic eigenmodes,' using autocovariance matrix decomposition and all poles power spectral and wavelet transformations. L-or D-amino acid (retro-inverso) 12-18 residue peptides targeting these modes can be designed using eigenvector templates derived from these computations. In all, 12 human long-form D 2 dopamine receptor eigenmode-targeted 15 mer peptides were designed, synthesized, and shown to modulate and/or indirectly activate the extracellular acidification response, EAR, in stably receptor-transfected CHO and LtK cells, with an 83% hit rate. Representative L-and D-amino-acid retro-inverso peptides injected bilaterally in the nucleus accumbens demonstrated changes in rat exploratory behavior and prepulse inhibition similar to those observed following parenteral amphetamine. In contrast with geometric models used for ligand design, such as pharmacophores, the hydrophobic eigenmode approach to lead modulatory peptide design targets hydrophobic eigenmode-bearing subsequences, including those not visible from X-ray and NMR studies such as extracellular segments and loops.

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“…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. 7 We have consistently used 64,65 the earliest complete set of hydrophobic amino acid energetic transformations, the Tanford hydrophobicity scale in kcal/mol.…”

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

confidence: 99%

“…7,62 Subsequent work confirmed the usefulness of wavelet transformation in locating transmembrane segments, as well as the hydrophobic core and repeating motifs in globular proteins. 9,11,63 Using standard methods, 59,60 the continuous Morlet wavelet transformations of the first and second eigenfunctions of GAL were computed and displayed as phase amplitude plots in Figures 2A and 2B and 3. The sequence positions (uncorrected for the offset created by the 14-lagged autocovariance matrix generating the eigenvectors and thus the eigenfunctions) are indicated along the x-axis.…”

Section: Data Relevant To Gal's Hydrophobic Eigenmode Accessibility Amentioning

confidence: 99%

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Designing allosteric peptide ligands targeting a globular protein

et al. 2006

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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

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Wavelet transforms for the characterization and detection of repeating motifs

Cited by 92 publications

References 45 publications

Global characteristics of protein sequences and their implications

Global characteristics of protein sequences and their implications

Cellular and Behavioral Effects of D2 Dopamine Receptor Hydrophobic Eigenmode-Targeted Peptide Ligands

Designing allosteric peptide ligands targeting a globular protein

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