TCBG Seminar

Simulating nucleic acid molecules and nucleic acid protein complexes

PI Karissa Sanbonmatsu
Theoretical Biology & Biophysics
Los Alamos National Lab
Los Alamo, NM

Monday, December 6, 2021
3:00 pm (CT)
Zoom webinar link


Since 2001, our long-term goal has been to understand the kinetics and thermodynamics of tRNA translocation through the ribosome, arguably the most complex of all ribosome conformational changes. We have used a variety of techniques to simulate movement of tRNA into the ribosome during tRNA selection and through the ribosome during tRNA translocation. Using a combination of explicit solvent molecular dynamics simulations and all-atom structure- based simulations, we simulate spontaneous accommodation events of tRNA into and out of the aminoacyl site, producing sufficient sampling for energy landscapes. As a first step towards obtaining energy landscapes of translocation, configurations of the ribosome relevant to translocation were modeled. Following this step, using a combination of targeting and structure- based models, several sub-steps of tRNA translocation through the ribosome were simulated, including 30S rotation, hybrid state formation and head swivel. We identified the universally conserved accommodation corridor and hybrid state corridor, delineating regions on the large subunit critical for transport of the tRNA 3-CCA ends through the ribosome. To help improve our technology for RNA simulation, we also perform structure-based and explicit solvent simulations of riboswitch RNAs. Here, we have performed combined computational and experimental studies of the SAM-I and SAM-II riboswitches, focusing on the effect of magnesium on the RNA energy landscape. We have performed detailed calculations of the free energy landscape as a function of ion concentrations, demonstrating that ions pre-organize the RNA before it achieves its fully collapsed, native conformation. We obtained agreement with experiments and with explicit solvent simulations.

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