PEOPLE: CURRENT LAB MEMBERS

Lucas Nivon
Graduate Student
Department of Chemistry and Chemical Biology
Harvard University
12 Oxford St.
Cambridge, MA 02138
Tel: (617) 384-9078   
Fax: (617) 384-9228
nivon@fas.harvard.edu
web site

Research Summary

Monte Carlo RNA Folding Simulation

Molecular Dynamics (MD) simulation attempt to bridge the gap between theory and experiment in biopolymer folding, but require prohibitively large amounts of computational time. Monte Carlo (MC) simulation provide a method to sample conformational space rapidly and in a thermodynamically accurate way. MC with a purely torsional move set and Go potential has been shownt o fold proteins with correct thermodynamics and realistic kinetics. We are applying a similar simulation algorithm to the RNA folding problem, using a torsional move set and a Go potential. At each step, a move is taken, the new conformation is checked for clashes and the energy of the new conformation is evaluated. Steps are accepted according to the metropolis MC criterion. We used this to study the folding the GCAA RNA tetraloop. A sharp folding transtion was observed, with evidence suggesting a distinct short-lived intermediate along the "zipping" pathway of hairpin folding (Nivon and Shakhnovich, J. Mol. Biol. vol. 344, pp. 29-45).

[A more extensive description can be found in the attached pdf] We are extending this work to the study of the folding of larger ribozyme RNAs, such as the hairpin ribozyme, and are studying modified versions of the Go and other, less-biased knowledge-based potentials.