| Abstract
| - NMR-observable scalar couplings across hydrogen bonds in nucleic acids and proteins presenta quantitative measure for the geometry and by the implicit experimental time averaging dynamics ofhydrogen bonds. We have carried out in-depth molecular dynamics (MD) simulations with various forcefields on three proteins: ubiquitin, the GB1 domain of protein G, and the SMN Tudor domain, for whichexperimental h3JNC‘ scalar couplings of backbone hydrogen bonds and various high-resolution X-raystructures are available. Theoretical average values for h3JNC‘ were calculated from the snapshots of theseMD simulations either by density functional theory or by a geometric parametrization (Barfield, M. J. Am.Chem. Soc.2002, 124, 4158−4168). No significant difference was found between the two methods. Theresults indicate that time-averaging using explicit water solvation in the MD simulations improves significantlythe agreement between experimental and theoretical values for the lower resolution structures ubiquitin(1.8 Å), Tudor domain (1.8 Å), and protein G (2.1 Å). Only marginal improvement is found for the high-resolution structure (1.1 Å) of protein G. Hence, experimental h3JNC‘ values are compatible with a static,high-resolution structural model. The MD averaging of the low-resolution structures moves the averagesof the rHO distance and the H···OC angle θ closer to their respective values in the high-resolution structures,thereby improving the agreement using experimental h3JNC‘ data. In contrast, MD averaging with implicitwater models deteriorates the agreement with experiment for all proteins. The differing behavior can beexplained by an artifactual lengthening of H-bonds caused by the implicit water models.
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