Premium
Global and local motions in ribonuclease A: A molecular dynamics study
Author(s) -
Merlino Antonello,
Vitagliano Luigi,
Antoine Ceruso Marc,
Di Nola Alfredo,
Mazzarella Lelio
Publication year - 2002
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.10225
Subject(s) - rnase p , molecular dynamics , protein dynamics , chemistry , ribonuclease , rnase h , active site , dynamics (music) , function (biology) , crystallography , binding site , enzyme , biophysics , stereochemistry , physics , computational chemistry , biochemistry , genetics , rna , biology , acoustics , gene
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 β‐sheet regions of RNase A move coherently in opposite directions, thus modifying solvent accessibility of the active site, and that the mixed α/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. © 2002 Wiley Periodicals, Inc. Biopolymers 65: 274–283, 2002