title: Unravelling Protein-DNA Interactions at Molecular Level: A DFT and NCI Study.
abstract: Histone-DNA interactions were probed computationally at a molecular level, by characterizing the bimolecular clusters constituted by selected amino acid derivatives with polar (asparagine and glutamine), nonpolar (alanine, valine, and isoleucine), and charged (arginine) side chains and methylated pyrimidinic (1-methylcytosine and 1-methylthymine) and puric (9-methyladenine and 9-methylguanine) DNA bases. The computational approach combined different methodologies: a molecular mechanics (MMFFs forced field) conformational search and structural and vibrational density-functional calculations (M06-2X with double and triple-ζ Pople's basis sets). To dissect the interactions, intermolecular forces were analyzed with the Non-Covalent Interactions (NCI) analysis. The results for the 24 different clusters studied show a noticeable correlation between the calculated binding energies and the propensities for protein-DNA base interactions found in the literature. Such correlation holded even for the interaction of the selected amino acid derivatives with Watson and Crick pairs. Therefore, the balance between hydrogen bonds and van der Waals interactions (specially stacking) in the control of the final shape of the investigated amino acid-DNA base pairs seems to be well reproduced in dispersion-corrected DFT molecular models, reinforcing the idea that the specificity between the amino acids and the DNA bases play an important role in the regulation of DNA.
authors.affiliation: Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco-UPV/EHU , Barrio Sarriena s/n, Leioa, 48940 Spain.
authors.forename: J
authors.initials: J
authors.lastname: González
authors.affiliation: Departamento de Química, Facultad de Ciencias, Estudios Agroalimentarios e Informática, Universidad de La Rioja , Madre de Dios, 53, Logroño, 26006 Spain.
authors.forename: I
authors.initials: I
authors.lastname: Baños
authors.affiliation: Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco-UPV/EHU , Barrio Sarriena s/n, Leioa, 48940 Spain.
authors.forename: I
authors.initials: I
authors.lastname: León
authors.affiliation: Sorbonne Universités, UPMC Univ. Paris 06, UMR7616, Laboratoire de Chimie Théorique, F-75005, Paris, France.|CNRS, UMR 7616, Laboratoire de Chimie Théorique, F-75005, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Contreras-García
authors.affiliation: Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco-UPV/EHU , Barrio Sarriena s/n, Leioa, 48940 Spain.
authors.forename: E J
authors.initials: EJ
authors.lastname: Cocinero
authors.affiliation: Departamento de Química Física y Química Inorgánica, Facultad de Ciencias, Universidad de Valladolid , 47011 Valladolid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Lesarri
authors.affiliation: Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco-UPV/EHU , Barrio Sarriena s/n, Leioa, 48940 Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Fernández
authors.affiliation: Departamento de Química, Facultad de Ciencias, Estudios Agroalimentarios e Informática, Universidad de La Rioja , Madre de Dios, 53, Logroño, 26006 Spain.
authors.forename: J
authors.initials: J
authors.lastname: Millán
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D020029:Base Pairing; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011789:Quantum Theory; D055672:Static Electricity
chemical_list: D000596:Amino Acids; D006657:Histones; D004247:DNA