Side-chain conformational libraries

The second approach to dealing with poor data is the use of standard conformation libraries [3], It is clear that the use of perfect coordinates in such libraries to help building the model is to be preferred over coordinates with errors. However, there is one danger in the use of standard libraries circularity. Take, for example, side chain conformation libraries [3,18,19]. Residues positioned in a structure purely based on such a database will not easily be flagged as incorrect by rotamer... 

The course of the WHAT CHECK structural Z-scores throughout the past 10 years is depicted in Fig. 5. In this analysis, we determined several global Z-scores for all the structures solved in the past 10 years with a resolution between 1.8 and 2.2 A, by using the internal WHAT CHECK database generated in 2000. It can be seen from Fig. 5 that the chi-1/chi-2 rotamer distribution, in particular, has improved over the years, which is most likely due to the use of side-chain conformation libraries in structure determination. The other structural Z-scores show an insignificantly small... 

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. 

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... 

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 ... 

Tuffery and co-workers have used GAs to treat the problem of determining side chain conformations for a protein when the backbone conformation is fixed. Their approach is to draw side chains from a rotamer library and fit them together in an optimal way. Each amino acid side chain is represented... 

The rotamer library used by SCWRL is backbone-dependent. Such libraries are considered to be more accurate than a backbone-independent rotamer library. A backbone-dependent rotamer library is more robust because the side-chain conformations are based on the protein s backbone dihedral angles ( and Both the secondary structure and the... 

A. D. Scouras and V. Daggett, Protein Sci., 20, 341 (2011). The Dynameomics Rotamer Library Amino Acid Side Chain Conformations and Dynamics from Comprehensive Molecular Dynamics Simulations in Water. 

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