New Monte Carlo Based Technique To Study DNA–Ligand Interactions
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European Commission's projectPELE - P.E.L.E (Protein Energy Landscape Exploration): a la carte drug design tools (EC-FP7-250277)
We present a new all-atom Monte Carlo technique capable of performing quick and accurate DNA–ligand conformational sampling. In particular, and using the PELE software as a frame, we have introduced an additional force field, an implicit solvent, and an anisotropic network model to effectively map the DNA energy landscape. With these additions, we successfully generated DNA conformations for a test set composed of six DNA fragments of A-DNA and B-DNA. Moreover, trajectories generated for cisplatin and its hydrolysis products identified the best interacting compound and binding site, producing analogous results to microsecond molecular dynamics simulations. Furthermore, a combination of the Monte Carlo trajectories with Markov State Models produced noncovalent binding free energies in good agreement with the published molecular dynamics results, at a significantly lower computational cost. Overall our approach will allow a quick but accurate sampling of DNA–ligand interactions.
CitationCabeza de Vaca, Israel; Lucas, Fatima; Guallar, Víctor. New Monte Carlo Based Technique To Study DNA–Ligand Interactions. "Journal of Chemical Theory and Computation", 03 Novembre 2015, vol. 11, núm. 12, p. 5598-5605.
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