Molecular Dynamics Simulation of the Conformational Preferences of Pseudouridine Derivatives: Improving the Distribution in the Glycosidic Torsion Space.

摘要: There are only four derivatives of pseudouridine (Ψ) that known to occur naturally in RNA as post-transcriptional modifications. We have studied the conformational consequences pseudouridylation and further modifications using replica exchange molecular dynamics simulations at nucleoside level, simulated preferences were compared with available experimental (NMR) data. found existing AMBER FF99-derived parameters for these nucleosides did not reproduce observed features while recommended bsc0 correction could be combined leading an improvement description sugar pucker distributions, χOL3 applied such because base isomerization. On other hand, revised χ torsion (χIDRP) Ψ developed earlier by us (Deb, I., J. Comput. Chem., 2016, 37, 1576-1588) combination provided γ generated which generally better agreement A significant shift distribution orientation toward syn conformation was our parameter sets large excess anti predicted FF99 parameters. Overall, observations indicated set also able generate distributions all