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. 1985 Dec;82(24):8458–8462. doi: 10.1073/pnas.82.24.8458

Active site dynamics of ribonuclease.

A T Brünger, C L Brooks 3rd, M Karplus
PMCID: PMC390935  PMID: 3866234

Abstract

The stochastic boundary molecular dynamics method is used to study the structure, dynamics, and energetics of the solvated active site of bovine pancreatic ribonuclease A. Simulations of the native enzyme and of the enzyme complexed with the dinucleotide substrate CpA and the transition-state analog uridine vanadate are compared. Structural features and dynamical couplings for ribonuclease residues found in the simulation are consistent with experimental data. Water molecules, most of which are not observed in crystallographic studies, are shown to play an important role in the active site. Hydrogen bonding of residues with water molecules in the free enzyme is found to mimic the substrate-enzyme interactions of residues involved in binding. Networks of water stabilize the cluster of positively charged active site residues. Correlated fluctuations between the uridine vanadate complex and the distant lysine residues are mediated through water and may indicate a possible role for these residues in stabilizing the transition state.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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