Rotamer library

Dunbrack R L Jr and M Karplus 1993. Backbone-dependent Rotamer Library for Proteins. Applic to Side-chain Prediction. Journal of Molecular Biology 230 543-574. 

MJ Bower, FE Cohen, RL Dunbrack Jr. Prediction of protein side-chain rotamers from a backbone-dependent rotamer library A new homology modeling tool. J Mol Biol 267 1268-1282, 1997. 

RL Dunbrack, M Karplus. Pi ediction of protein side-chain conformations from a backbone conformation dependent rotamer library. J Mol Biol 230 543-571, 1993. 

Analysis and prediction of side-chain conformation have long been predicated on statistical analysis of data from protein structures. Early rotamer libraries [91-93] ignored backbone conformation and instead gave the proportions of side-chain rotamers for each of the 18 amino acids with side-chain dihedral degrees of freedom. In recent years, it has become possible to take account of the effect of the backbone conformation on the distribution of side-chain rotamers [28,94-96]. McGregor et al. [94] and Schrauber et al. [97] produced rotamer libraries based on secondary structure. Dunbrack and Karplus [95] instead examined the variation in rotamer distributions as a function of the backbone dihedrals ( ) and V /, later providing conformational analysis to justify this choice [96]. Dunbrack and Cohen [28] extended the analysis of protein side-chain conformation by using Bayesian statistics to derive the full backbone-dependent rotamer libraries at all... 

MJ McGregor, SA Islam, MJE Sternberg. Analysis of the relationship between sidecham conformation and secondary stiaicture m globular proteins. J Mol Biol 198 295-310, 1987. RL Dunbrack Jr, M Karplus. Backbone-dependent rotamer library for proteins Application to sidecham prediction. J Mol Biol 230 543-571, 1993. 

Certain side-chain conformations are energetically mote favorable than others. Computer programs used to model protein structures contain rotamer libraries of such favored conformations. 

If the sequence of a protein has more than 90% identity to a protein with known experimental 3D-stmcture, then it is an optimal case to build a homologous structural model based on that structural template. The margins of error for the model and for the experimental method are in similar ranges. The different amino acids have to be mutated virtually. The conformations of the new side chains can be derived either from residues of structurally characterized amino acids in a similar spatial environment or from side chain rotamer libraries for each amino acid type which are stored for different structural environments like beta-strands or alpha-helices. 

Dunbrack, R.L. Jr. Rotamer libraries in the 21st century. Curr. Opin. Struct. Biol. 2002,12,431 10. 

King et al. (292)used an empirical binding Ifee-energy function when docking MVT-101 to HIV protease. Forty-nine translation/rota-tions were examined with the Ponder/Richard rotamer library. Only a limited number of retainers for each amino acid were examined Thr(2), Ile(3), Nle(3), Nle(3), Gln(6), and Arg(5). According to the authors, 2.24 x 10 ° discrete states were examined. Sixty-four low ener structures with an average rmsd of 1.36 A were found. If the CHARMM potential was used with the same protocol, then the av-eragQ rmsd was increased to 1.68 A. 

Side-chains were substituted to match the sequence of the Fv R45. We set up the dihedral angles x 1 and x2 (Table I) according to the highest probability found in the rotamer library established by Tuffery et al. (1991). Dihedral angles x3 and x4 were set to 180°. Consequently, each amino acid side chain displays the same starting conformation. 

Dunbrack, R.L., Jr. and Karplus, M. (1993) Backbone-dependent rotamer library for proteins. Application to side-chain prediction, J. Mol. Biol. 230, 543-574. 

Dunbrack RL (2002) Rotamer libraries in the 21st century. Curr Opin Struct Biol 12 431-440 Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28 235-242... 

Moult, James, Fidelis [126, 135] Rotamer library, complete search Electrostatic term, image-charge solvation term, van der Waals, hydrophobic term... 

Reduced side-chain model of Levitt CB-only in minimization of initial loops later bbdep rotamer library None... 

Abbreviations used in table MC - Monte Carlo aa - amino acid vdW - van der Waals potential Ig - immunoglobulin or antibody CDR - complementarity-determining regions in antibodies RMS -root-mean-square deviation r-dependent dielectric - distance-dependent dielectric constant e - dielectric constant MD - molecular dynamics simulation self-loops - prediction of loops performed by removing loops from template structure and predicting their conformation with template sequence bbdep - backbone-dependent rotamer library SCMF - self-consistent mean field PDB - Protein Data Bank Jones-Thirup distances - interatomic distances of 3 Ca atoms on either side of loop to be modeled. 

As crystal structures of proteins have been solved in increasing numbers, a variety of rotamer libraries have been compiled with increasing amounts of detail and greater statistical soundness that is, with more structures at higher resolution [160-169]. The earliest rotamer libraries were based on a small number of structures [160-163]. Even the widely used Ponder Richards library was based on only 19 structures, including only 16 methionines [163], The most recent libraries are based on over 600 structures with resolution of 1.8 A or better and mutual sequence identity less than 50% between any two chains used. 

Most rotamer libraries are backbone-conformation-independent. In these libraries, the dihedral angles for side chains are averaged over all side chains of a given type and rotamer class, regardless of the local backbone conformation or secondary structure. These libraries include two in common use in side-chain conformation prediction methods, that of Ponder Richards and that of Tuffery et al. [165], It should be noted that the Ponder-Richards library is based on a very small sample of proteins and should not be used for conformation prediction (which was not its intended use anyway). The Tuffery library is based on 53 structures, which is also a very small sample compared to the PDB now available. Kono and Doi also published a rotamer... 

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