Side 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... 

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. 

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. 

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. 

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... 

Side-chain prediction methods can be classified in terms of how they treat side-chain dihedral angles (rotamer library, grid, or continuous dihedral angle distribution), potential energy function used to evaluate proposed conformations, and search strategy. These factors are summarized in Table... 

SCWRL uses an alternative strategy, based on a probabilistic potential based on the backbone-dependent rotamer library. There are two terms the internal side-chain energy and the local side-chain-backbone interaction are modeled with an energy term proportional to —In prot where prot is the probability of the rotamer for the particular side-chain type and backbone conformation and a simple truncated linear steric term that models the repulsive interactions between atoms [93, 94]. 

Alternatively, one tries to extrapolate the correct rotamer from examples of residues in a similar environment in the database of known structures. The main problem here is how to define similar environments. In practice, similar environments for residues have most often been defined as having the same secondary structure (a-helix, P-strand, or loop). Until recently, side chains were normally placed using standard rotamer libraries [28-30]. A variety of procedures have been used to get rid of van der Waals clashes. These range from manual... 

The latest developments in modeling are position-specific rotamer searches (Fig. 2). Dunbrack et al. and Vriend et al. showed that the preferred rotamer is to a large extent determined by a local backbone [34,35], Database searches for peptides with the same local backbone and the same amino acid type in the middle often reveal a more restricted pattern of side-chain conformations than one would expect from generalized rotamer libraries. Position-specific rotamer distributions are obtained by searching the database for segments of residues that fulfill two criteria ... 

Correctly orientating side-chains Side-chain orientation is strongly dependent upon backbone conformation and local environmental featiues. Thus, the accuracy of side-chain placement in the model will depend upon the accuracy of the backbone. In general, in comparative modelling the most accurate placement of side-chains is achieved with the use of rotamer libraries (e.g. Lovell et al. Dunbrack and Karplus ). 

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