Molecular dynamics simulations of ribonuclease T1: comparison of the free enzyme and the 2' GMP-enzyme complex.

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TitleMolecular dynamics simulations of ribonuclease T1: comparison of the free enzyme and the 2' GMP-enzyme complex.
Publication TypeJournal Article
Year of Publication1989
AuthorsMackerell, AD, Nilsson, L, Rigler, R, Heinemann, U, Saenger, W
Date Published1989
KeywordsBinding Sites, Computer Simulation, Endoribonucleases, Fluorescence Polarization, Fungal Proteins, Guanine Nucleotides, Guanosine Monophosphate, Models, Molecular, Protein Binding, Protein Conformation, Ribonuclease T1, Tryptophan, Tyrosine, X-Ray Diffraction

Molecular dynamics simulations were performed on free RNase T1 and the 2'GMP-RNase T1 complex in vacuum and with water in the active site along with crystallographically identified waters, allowing analysis of both active site and overall structural and dynamics changes due to the presence of 2'GMP. Differences in the active site include a closing in the presence of 2'GMP, which is accompanied by a decrease in mobility of active site residues. The functional relevance of the active site fluctuations is discussed. 2'GMP alters the motion of Tyr-45, suggesting a role for that residue in providing a hydrophobic environment for the protein-nucleic acid interactions responsible for the specificity of RNase T1. The presence of 2'GMP causes a structural change of the C-terminus of the alpha-helix, indicating the transmission of structural changes from the active site through the protein matrix. Overall fluctuations of both the free and 2'GMP enzyme forms are in good agreement with X-ray temperature factors. The motion of Trp-59 is influenced by 2'GMP, indicating differences in enzyme dynamics away from the active site, with the calculated changes following those previously seen in time-resolved fluorescence experiments.

Alternate JournalProteins
PubMed ID2558378