The penultimate rotamer library

Abstract

All published rotamer libraries contain some rotamers that exhibit impossible internal atomic overlaps if built in ideal geometry with all hydrogen atoms. Removal of uncertain residues (mainly those with B‐factors ≥40 or van der Waals overlaps ≥0.4 Å) greatly improves the clustering of rotamer populations. Asn, Gln, or His side chains additionally benefit from flipping of their planar terminal groups when required by atomic overlaps or H‐bonding. Sensitivity to skew and to the boundaries of χ angle bins is avoided by using modes rather than traditional mean values. Rotamer definitions are listed both as the modal values and in a preferred version that maximizes common atoms between related rotamers. The resulting library shows significant differences from previous ones, differences validated by considering the likelihood of systematic misfitting of models to electron density maps and by plotting changes in rotamer frequency with B‐factor. Few rotamers now show atomic overlaps in ideal geometry; those overlaps are relatively small and can be understood in terms of bond angle distortions compensated by favorable interactions. The new library covers 94.5% of examples in the highest quality protein data with 153 rotamers and can make a significant contribution to improving the accuracy of new structures. Proteins 2000;40:389–408. © 2000 Wiley‐Liss, Inc.

Chiral 3-(4,5-dihydrooxazol-2-yl)phenyl alkylcarbamates as novel FAAH inhibitors: Insight into FAAH enantioselectivity by molecular docking and interaction fields

“…Missing side chain atoms were added into the FAAH monomer (chain A extracted from the X-ray data) of the crystal structure by using Lovell rotamer library [65] and optimized in polarizable AMBER07_FF02 force field [66] (energy gradient of 0.01 kcal/mol) while keeping the rest of the protein atoms fixed, as implemented in Sybyl 8.1 [67]. Hydrogen atoms were added with MolProbity (v. 3.15) [68] server by allowing the program to optimize hydrogen bonding by flipping Asn, Gln or His, where applicable.…”

Site-directed circular dichroism of proteins: 1Lb bands of Trp resolve position-specific features in tear lipocalin

“…The energetically favorable rotamer (g − (−60°; +90°)) of Trp87 and the residues in the flanking β-strands are shown in Figure 9. Analysis of the distribution of Trp rotamers in globular proteins show that the rotamer g − is the most favorable [37,38] in β-strands, particularly at the center of β-strands [38]. It is interesting to note that the estimated contribution of the tryptophan side chain (B b rotational strength) in the g − (−60°; +90°) conformation to the far-UV CD is −0.39 DBM (Debye-Bohr magneton, 1 DBM= 0.9273 × 10 −38 cgs units) [28], which corroborates the far-UV CD data for the TL mutants.…”

An Automated System for the Analysis of G Protein-Coupled Receptor Transmembrane Binding Pockets: Alignment, Receptor-Based Pharmacophores, and Their Application

“…These values were derived from the statistical analysis of a rotamer library. 63 Features with H-bond donor or H-bond acceptor properties are assigned a cone pointing toward the most likely direction of the H bond. The angle for the cone opening indicates a measure for the direction of the H bond.…”

“…From standard rotamer conformations, the positions of relevant atoms for each amino acid side chain were averaged by taking into account the relative frequencies of the rotamers found in R helices from a recently published rotamer library. 63 These average positions are listed in Table 2, where all values are reported within the local coordinate system introduced above. They were used as starting points for the empirical generation of an optimum spherical representation of the amino acid side chains.…”