Identifying sequence-structure pairs undetected by sequence alignments.

We examine how effectively simple potential functions previously developed can identify compatibilities between sequences and structures of proteins for database searches. The potential function consists of pairwise contact energies, repulsive packing potentials of residues for overly dense arrangement and short-range potentials for secondary structures, all of which were estimated from statistical preferences observed in known protein structures. Each potential energy term was modified to represent compatibilities between sequences and structures for globular proteins. Pairwise contact interactions in a sequence-structure alignment are evaluated in a mean field approximation on the basis of probabilities of site pairs to be aligned. Gap penalties are assumed to be proportional to the number of contacts at each residue position, and as a result gaps will be more frequently placed on protein surfaces than in cores. In addition to minimum energy alignments, we use probability alignments made by successively aligning site pairs in order by pairwise alignment probabilities. The results show that the present energy function and alignment method can detect well both folds compatible with a given sequence and, inversely, sequences compatible with a given fold, and yield mostly similar alignments for these two types of sequence and structure pairs. Probability alignments consisting of most reliable site pairs only can yield extremely small root mean square deviations, and including less reliable pairs increases the deviations. Also, it is observed that secondary structure potentials are usefully complementary to yield improved alignments with this method. Remarkably, by this method some individual sequence-structure pairs are detected having only 5-20% sequence identity.

[1]  M. Sippl.  Calculation of conformational ensembles from potentials of mean force. An approach to the knowledge-based prediction of local structures in globular proteins. , 1990, Journal of molecular biology.

[2]  S. Karlin,et al.  Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Feller William,et al.  An Introduction To Probability Theory And Its Applications , 1950 .

[4]  S. Bryant,et al.  An empirical energy function for threading protein sequence through the folding motif , 1993, Proteins.

[5]  G J Barton,et al.  Evaluation and improvements in the automatic alignment of protein sequences. , 1987, Protein engineering.

[6]  C Sander,et al.  Prediction of protein structure by evaluation of sequence-structure fitness. Aligning sequences to contact profiles derived from three-dimensional structures. , 1993, Journal of molecular biology.

[7]  F. Young.  Biochemistry , 1955, The Indian Medical Gazette.

[8]  O. Gotoh,et al.  Optimal sequence alignment allowing for long gaps. , 1990, Bulletin of mathematical biology.

[9]  M. Sippl.  Recognition of errors in three‐dimensional structures of proteins , 1993, Proteins.

[10]  M Levitt,et al.  Recognizing native folds by the arrangement of hydrophobic and polar residues. , 1995, Journal of molecular biology.

[11]  S. Henikoff,et al.  Amino acid substitution matrices from protein blocks. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[12]  P. Munson,et al.  Statistical significance of hierarchical multi‐body potentials based on Delaunay tessellation and their application in sequence‐structure alignment , 1997, Protein science : a publication of the Protein Society.

[13]  Alexei V. Finkelstein,et al.  A search for the most stable folds of protein chains , 1991, Nature.

[14]  K. Dill,et al.  An iterative method for extracting energy-like quantities from protein structures. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M Levitt,et al.  Alignment of the amino acid sequences of distantly related proteins using variable gap penalties. , 1986, Protein engineering.

[16]  Temple F. Smith,et al.  Global optimum protein threading with gapped alignment and empirical pair score functions. , 1996, Journal of molecular biology.

[17]  Janet M. Thornton,et al.  Protein fold recognition , 1993, J. Comput. Aided Mol. Des..

[18]  S. Wodak,et al.  Factors influencing the ability of knowledge-based potentials to identify native sequence-structure matches. , 1994, Journal of molecular biology.

[19]  M. Levitt,et al.  Energy functions that discriminate X-ray and near native folds from well-constructed decoys. , 1996, Journal of molecular biology.

[20]  Y. Matsuo,et al.  Protein structural similarities predicted by a sequence‐structure compatibility method , 1994, Protein science : a publication of the Protein Society.

[21]  S. Miyazawa,et al.  Relationship between mutability, polarity and exteriority of amino acid residues in protein evolution. , 2009, International journal of peptide and protein research.

[22]  P. Kraulis.  A program to produce both detailed and schematic plots of protein structures , 1991 .

[23]  T. Smith,et al.  Alignment of protein sequences using secondary structure: a modified dynamic programming method. , 1990, Protein engineering.

[24]  Y. Matsuo,et al.  Development of pseudoenergy potentials for assessing protein 3-D-1-D compatibility and detecting weak homologies. , 1993, Protein engineering.

[25]  E S Huang,et al.  Factors affecting the ability of energy functions to discriminate correct from incorrect folds. , 1997, Journal of molecular biology.

[26]  S. Miyazawa.  A reliable sequence alignment method based on probabilities of residue correspondences. , 1995, Protein engineering.

[27]  Alignment of protein sequences using the hydrophobic core scores. , 1989, Protein engineering.

[28]  T. Smith,et al.  Optimal sequence alignments. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[29]  M Vendruscolo,et al.  Efficient dynamics in the space of contact maps. , 1998, Folding & design.

[30]  K Nishikawa,et al.  Detection of protein 3D-1D compatibility characterized by the evaluation of side-chain packing and electrostatic interactions. , 1995, Journal of biochemistry.

[31]  R. Kretsinger,et al.  Refinement of the structure of carp muscle calcium-binding parvalbumin by model building and difference Fourier analysis. , 1976, Journal of molecular biology.

[32]  G. Casari,et al.  Identification of native protein folds amongst a large number of incorrect models. The calculation of low energy conformations from potentials of mean force. , 1990, Journal of molecular biology.

[33]  M S Waterman,et al.  Sequence alignment and penalty choice. Review of concepts, case studies and implications. , 1994, Journal of molecular biology.

[34]  G. Crippen.  Prediction of protein folding from amino acid sequence over discrete conformation spaces. , 1991, Biochemistry.

[35]  L A Mirny,et al.  How to derive a protein folding potential? A new approach to an old problem. , 1996, Journal of molecular biology.

[36]  R. Samudrala,et al.  An all-atom distance-dependent conditional probability discriminatory function for protein structure prediction. , 1998, Journal of molecular biology.

[37]  A G Murzin,et al.  SCOP: a structural classification of proteins database for the investigation of sequences and structures. , 1995, Journal of molecular biology.

[38]  G. Crippen,et al.  Contact potential that recognizes the correct folding of globular proteins. , 1992, Journal of molecular biology.

[39]  R. Jernigan,et al.  An empirical energy potential with a reference state for protein fold and sequence recognition , 1999, Proteins.

[40]  W R Taylor,et al.  Protein structure alignment. , 1989, Journal of molecular biology.

[41]  Sanzo Miyazawa,et al.  Evaluation of short‐range interactions as secondary structure energies for protein fold and sequence recognition , 1999, Proteins.

[42]  A. Godzik,et al.  Topology fingerprint approach to the inverse protein folding problem. , 1992, Journal of molecular biology.

[43]  R. Jernigan,et al.  Residue-residue potentials with a favorable contact pair term and an unfavorable high packing density term, for simulation and threading. , 1996, Journal of molecular biology.

[44]  W. Taylor,et al.  Multiple sequence threading: an analysis of alignment quality and stability. , 1997, Journal of molecular biology.

[45]  M. Sippl,et al.  Detection of native‐like models for amino acid sequences of unknown three‐dimensional structure in a data base of known protein conformations , 1992, Proteins.

[46]  D. T. Jones,et al.  A new approach to protein fold recognition , 1992, Nature.

[47]  R. Jernigan,et al.  Estimation of effective interresidue contact energies from protein crystal structures: quasi-chemical approximation , 1985 .

[48]  D. Eisenberg,et al.  Assessment of protein models with three-dimensional profiles , 1992, Nature.

[49]  C. Tanford.  Macromolecules , 1994, Nature.

[50]  S. B. Needleman,et al.  A general method applicable to the search for similarities in the amino acid sequence of two proteins. , 1970, Journal of molecular biology.

[51]  M. O. Dayhoff,et al.  Atlas of protein sequence and structure , 1965 .

[52]  R. Jernigan,et al.  Self‐consistent estimation of inter‐residue protein contact energies based on an equilibrium mixture approximation of residues , 1999, Proteins.