Global and local motions in ribonuclease A: a molecular dynamics study

The understanding of protein dynamics is one of the major goals of
structural biology. A direct link between protein dynamics and function has
been provided by x-ray studies performed on ribonuclease A (RNase A) (B. F.
Rasmussen et al., Nature, 1992, Vol. 357, pp. 423-424; L. Vitagliano et
al., Proteins: Structure, Function, and Genetics, 2002, Vol. 46, pp.
97-104). Here we report a 3 ns molecular dynamics simulation of RNase A in
water aimed at characterizing the dynamical behavior of the enzyme. The
analysis of local and global motions provides interesting insight on the
dynamics/function relationship of RNase A. In agreement with previous
crystallographic reports, the present study confirms that the RNase A
active site is constituted by rigid (His12, Asn44, Thr45) and flexible
(Lys41, Asp83, His119, Asp121) residues. The analysis of the global
motions, performed using essential dynamics, shows that the two beta-sheet
regions of RNase A move coherently in opposite directions, thus modifying
solvent accessibility of the active site, and that the mixed
alpha/3(10)-helix (residues 50-60) behaves as a mechanical hinge during the
breathing motion of the protein. These data demonstrate that this motion,
essential for RNase A substrate binding and release, is an intrinsic
dynamical property of the ligand-free enzyme.