DescriptionA longstanding goal of molecular simulations is to accurately predict the three-dimensional fold of a biopolymer given only knowledge of its primary sequence. Although recent work has demonstrated the successful folding of proteins ranging from 10-80 amino acids from the unfolded state, no comparable results exist for the folding of structured RNAs. In recent work, we have shown that this is a result of underlying inaccuracies in the energy model itself, due to underlying assumptions that work well for describing amino acids but are inapplicable for describing nucleic acids in solution. We have systematically corrected these biases in order to more accurately capture the inherent flexibility of single-stranded RNA loops, accurate base stacking energetics, and purine anti-syn interconversions. In a departure from traditional quantum chemistry-centric parameterization schemes, we calibrate the molecular mechanics potentials directly against the relevant thermodynamic and kinetic measurements of aqueous nucleosides and nucleotides. This application is to continue the kinetic, thermodynamic characterization of improved RNA force-field to enable de-novo RNA folding.
OrganizationSUNY at Albany
Sponsor Campus GridOSG-XSEDE
Principal Investigator
Alan Chen
Field Of ScienceMolecular and Structural Biosciences