Keywords: Essential Dynamics, Molecular Dynamics, Protein Dynamics, Protein Structure-Function, Ribonucleases, Enzymes, Solvents, X Rays, Ligands, Biopolymers, Asparagine, Aspartic Acid, Histidine, Lysine, Threonine, Water, Alpha Helix, Beta Sheet, Crystallography, Enzyme Active Site, Enzyme Substrate, Enzyme Substrate Complex, Nonhuman, Protein Function, Animals, Catalytic Domain, Cattle, Enzyme Stability, Models, Motion, Protein Conformation, Pancreatic, Thermodynamics,
Affiliations: *** IBB - CNR ***
Dipartimento di Chimica, Università degli Studi di Napoli Federico II, Via Cinthia, 80125 Napoli, Italy
Centro di Studio di Biocristallografia, CNR, Via Mezzocannone 6, 80134 Napoli, Italy
Department of Physiology and Biophysics, Mt Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 11104, United States
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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 its 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. (C) 2002 Wiley Periodicals, Inc.
Global and local motions in ribonuclease A: A molecular dynamics study