analyzed. Sixty one conformationally labile residues are identified in which side chains are displaced by >1 Å
in crystals of different space groups and/or are represented by pairs of alternative conformers in 11 crystal struc-
tures of RNase A. Polar and charged residues accessible to solvent predominate among them and are mostly
found in loop segments and in regions with distorted secondary structure, where steric constraints of the con-
formational freedom of side chains are decreased due to less tight packing. The population of the paired con-
formers is not enriched in torsionally strained (about the
1 angle) side chain conformations. In solution (1H
NMR data), the side chains of the majority of the conformationally labile residues are dynamically disor-dered to varying extent and move nearly stochastically. Most residues involved in complex formation with
RNase protein inhibitor are conformationally labile, and the rapidity of their stochastic fluctuations allows for
high rate of complex formation in solution. In the inner tightly packed regions, medium-scale fluctuations
important for crucial catalytic steps of covalent bond formation and breakage, and large-scale fluctuations
important for protein–protein interactions are observed along with small-amplitude vibrations.