title: New Monte Carlo Based Technique To Study DNA-Ligand Interactions.
abstract: 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.
authors.affiliation: Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona Supercomputing Center , c/Jordi Girona 29, 08034 Barcelona, Barcelona, Spain.
authors.forename: Israel
authors.initials: I
authors.lastname: Cabeza de Vaca
authors.affiliation: Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona Supercomputing Center , c/Jordi Girona 29, 08034 Barcelona, Barcelona, Spain.|Anaxomics Biotech, Balmes 89, 08008 Barcelona, Barcelona, Spain.
authors.forename: Maria Fátima
authors.initials: MF
authors.lastname: Lucas
authors.affiliation: Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona Supercomputing Center , c/Jordi Girona 29, 08034 Barcelona, Barcelona, Spain.|Institució Catalana de Recerca I Estudis Avançats, Passeig Lluís Companys 23, 08010 Barcelona, Barcelona, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Guallar
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D001665:Binding Sites; D002945:Cisplatin / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D044704:DNA, A-Form / Q000737:chemistry; D059371:DNA, B-Form / Q000737:chemistry; D008024:Ligands; D008390:Markov Chains; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D009690:Nucleic Acid Conformation
chemical_list: D044704:DNA, A-Form; D059371:DNA, B-Form; D008024:Ligands; D004247:DNA; D002945:Cisplatin