title: Global and local motions in ribonuclease A: a molecular dynamics study.
abstract: 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.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Napoli Federico II, Via Cinthia, 80125 Napoli, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Merlino
authors.forename: Luigi
authors.initials: L
authors.lastname: Vitagliano
authors.forename: Marc Antoine
authors.initials: MA
authors.lastname: Ceruso
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Nola
authors.forename: Lelio
authors.initials: L
authors.lastname: Mazzarella
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D002417:Cattle; D004795:Enzyme Stability; D066298:In Vitro Techniques; D008958:Models, Molecular; D009038:Motion; D011487:Protein Conformation; D012259:Ribonuclease, Pancreatic / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D012259:Ribonuclease, Pancreatic