#5 · Structural bio & protein design

Simulations Link RNA Modifications to Conformation and Electronic Structure

The common thread is the use of molecular dynamics and quantum mechanical methods to dissect how chemical modifications and cofactor chemistry alter nucleic acid conformation and electronic structure. A preprint applies MD, 3D-RISM, free-energy and QM/MM simulations to the SAM-utilizing SAMURI ribozyme, examining conformational preorganization and electronic effects governing RNA alkylation. A published study reports microsecond MD of hAGO2-siRNA complexes, in which seed-region modifications (2'-OMe, 2'-F, (S)-GNA, ANA) produce position-dependent effects. A second publication applies quantum mechanical calculations to tRNA U34 modifications, showing that s2U, mnm5U, mcm5U, mnm5s2U and mcm5s2U shift the electronic states and geometry of the wobble U•G pair. What is new is the explicit linkage of modification-dependent electronic and geometric changes to functional outcomes across distinct RNA contexts, spanning catalysis, RNAi, and decoding.