Analysis of a data set of paired uncomplexed protein structures: New metrics for side-chain flexibility and model evaluation

We compiled and analyzed a data set of paired protein structures containing proteins for which multiple high-quality uncomplexed atomic structures wer e available in the Protein Data Bank. Side-chain flexibility was quantified , yielding a set of residue- and environment-specific confidence levels des cribing the range of motion around X, and X, angles. As expected, buried re sidues were inflexible, adopting similar conformations in different crystal structure analyses. Ile, Thr, Asn, Asp, and the large aromatics also showe d limited flexibility when exposed on the protein surface, whereas exposed Ser, Lys, Arg, Met, Gin, and Glu residues were very flexible. This informat ion is different from and complementary to the information available from r otamer surveys. The confidence levels are useful for assessing the signific ance of observed side chain motion and estimating the extent of side-chain motion in protein structure prediction. We compare the performance of a sim ple 40 degrees threshold with these quantitative confidence levels in a cri tical evaluation of side-chain prediction with the program SCWRL. (C) 2001 Wiley-Liss, Inc.