Andante: reducing side-chain rotamer search space during comparative modeling using environment-specific substitution probabilities

MOTIVATION The accurate placement of side chains in computational protein modeling and design involves the searching of vast numbers of rotamer combinations. RESULTS We have applied the information contained within structurally aligned homologous families, in the form of conserved chi angle conservation rules, to the problem of the comparative modeling. This allows the accurate borrowing of entire side-chain conformations and/or the restriction to high probability rotamer bins. The application of these rules consistently reduces the number of rotamer combinations that need to be searched to trivial values and also reduces the overall side-chain root mean square deviation (rmsd) of the final model. The approach is complementary to current side-chain placement algorithms that use the decomposition of interacting clusters to increase the speed of the placement process.

[1]  M Delarue,et al.  The inverse protein folding problem: self consistent mean field optimisation of a structure specific mutation matrix. , 1997, Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing.

[2]  Roland L. Dunbrack,et al.  Bayesian statistical analysis of protein side‐chain rotamer preferences , 1997, Protein science : a publication of the Protein Society.

[3]  Roland L. Dunbrack,et al.  Prediction of protein side-chain rotamers from a backbone-dependent rotamer library: a new homology modeling tool. , 1997, Journal of molecular biology.

[4]  N Srinivasan,et al.  Stereochemical modeling of disulfide bridges. Criteria for introduction into proteins by site-directed mutagenesis. , 1989, Protein engineering.

[5]  T L Blundell,et al.  FUGUE: sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties. , 2001, Journal of molecular biology.

[6]  Charlotte M. Deane,et al.  JOY: protein sequence-structure representation and analysis , 1998, Bioinform..

[7]  M Karplus,et al.  Analysis of side-chain orientations in homologous proteins. , 1987, Journal of molecular biology.

[8]  John P. Overington,et al.  HOMSTRAD: A database of protein structure alignments for homologous families , 1998, Protein science : a publication of the Protein Society.

[9]  John P. Overington,et al.  Tertiary structural constraints on protein evolutionary diversity: templates, key residues and structure prediction , 1990, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[10]  Stephen L. Mayo,et al.  Conformational splitting: A more powerful criterion for dead-end elimination , 2000, J. Comput. Chem..

[11]  John P. Overington,et al.  Environment‐specific amino acid substitution tables: Tertiary templates and prediction of protein folds , 1992, Protein science : a publication of the Protein Society.

[12]  Maximiliano Vásquez,et al.  An evaluvation of discrete and continuum search techniques for conformational analysis of side chains in proteins , 1995 .

[13]  I. Lasters,et al.  The fuzzy-end elimination theorem: correctly implementing the side chain placement algorithm based on the dead-end elimination theorem. , 1993, Protein engineering.

[14]  Wei Xie,et al.  Residue-rotamer-reduction algorithm for the protein side-chain conformation problem , 2006, Bioinform..

[15]  J. Richardson,et al.  The penultimate rotamer library , 2000, Proteins.

[16]  C. Sander,et al.  Database algorithm for generating protein backbone and side-chain co-ordinates from a C alpha trace application to model building and detection of co-ordinate errors. , 1991, Journal of molecular biology.

[17]  Mona Singh,et al.  Solving and analyzing side-chain positioning problems using linear and integer programming , 2005, Bioinform..

[18]  Kenji Mizuguchi,et al.  HOMSTRAD: recent developments of the Homologous Protein Structure Alignment Database , 2004, Nucleic Acids Res..

[19]  Adrian A Canutescu,et al.  Access the most recent version at doi: 10.1110/ps.03154503 References , 2003 .

[20]  S. Subbiah,et al.  Prediction of protein side-chain conformation by packing optimization. , 1991, Journal of molecular biology.

[21]  Roland L. Dunbrack,et al.  Backbone-dependent rotamer library for proteins. Application to side-chain prediction. , 1993, Journal of molecular biology.

[22]  T. Blundell,et al.  Comparative protein modelling by satisfaction of spatial restraints. , 1993, Journal of molecular biology.

[23]  R. Lavery,et al.  A new approach to the rapid determination of protein side chain conformations. , 1991, Journal of biomolecular structure & dynamics.

[24]  H. Umeyama,et al.  The role played by environmental residues on sidechain torsional angles within homologous families of proteins: A new method of sidechain modeling , 1998, Proteins.

[25]  Christopher A. Voigt,et al.  Trading accuracy for speed: A quantitative comparison of search algorithms in protein sequence design. , 2000, Journal of molecular biology.

[26]  I Lasters,et al.  Enhanced dead-end elimination in the search for the global minimum energy conformation of a collection of protein side chains. , 1995, Protein engineering.

[27]  I Lasters,et al.  All in one: a highly detailed rotamer library improves both accuracy and speed in the modelling of sidechains by dead-end elimination. , 1997, Folding & design.

[28]  References , 1971 .

[29]  John P. Overington,et al.  Fragment ranking in modelling of protein structure. Conformationally constrained environmental amino acid substitution tables. , 1993, Journal of molecular biology.

[30]  D Eisenberg,et al.  A 3D-1D substitution matrix for protein fold recognition that includes predicted secondary structure of the sequence. , 1997, Journal of molecular biology.

[31]  T L Blundell,et al.  Knowledge based modelling of homologous proteins, Part II: Rules for the conformations of substituted sidechains. , 1987, Protein engineering.

[32]  D B Gordon,et al.  Branch-and-terminate: a combinatorial optimization algorithm for protein design. , 1999, Structure.

[33]  M Karplus,et al.  Construction of side-chains in homology modelling. Application to the C-terminal lobe of rhizopuspepsin. , 1989, Journal of molecular biology.

[34]  Jinbo Xu,et al.  Rapid Protein Side-Chain Packing via Tree Decomposition , 2005, RECOMB.

[35]  J. Ponder,et al.  Tertiary templates for proteins. Use of packing criteria in the enumeration of allowed sequences for different structural classes. , 1987, Journal of molecular biology.

[36]  M Karplus,et al.  Modeling of side chains, loops, and insertions in proteins. , 1991, Methods in enzymology.

[37]  Niles A Pierce,et al.  Protein design is NP-hard. , 2002, Protein engineering.

[38]  L L Looger,et al.  Generalized dead-end elimination algorithms make large-scale protein side-chain structure prediction tractable: implications for protein design and structural genomics. , 2001, Journal of molecular biology.

[39]  R. Goldstein.  Efficient rotamer elimination applied to protein side-chains and related spin glasses. , 1994, Biophysical journal.