New computational approaches to the simulation of nucleic acid interactions will be developed, including improved molecular mechanical force fields, new methods to calculate free energies and new methods to enhance conformational sampling. These new approaches will be applied to DNA and RNA the structures and the interactions of DNA and RNA with proteins and small molecule Iigands. The goal is to accurately reproduce experimental structures and free energies of binding in these systems when these are known. Applications include interactions of DNA with anticancer drug daunonycin and its analogs, minor groove topoisomerase I inhibitors which have anti-cancer activity, and polyamides which are among the most promising therapeutic approaches to target specific DNA sequences, as well as interactions of DNA with both binding proteins (the zinc finger Zif 268) and proteins that catalyze specific site cleavage of the DNA (Eco RV). Dr. Kollman will also study RNA-ligand interactions which are relevant in anti-viral and anti-AIDS chemotherapy, as well as elucidating the mechanism of catalysis of the ribosome, certainly the most important ribozyme yet discovered.
NIH ExPorter
NIH ExPorter