title: Investigating the effect of charged amino acids on DNA conformation in EcoRI-DNA complex: a molecular dynamics simulation study.
abstract: Sequence-specific binding of proteins to DNA is essential for almost all the cellular processes like transcription, translation, replication, etc. One among the various mechanisms that has been identified so far that contributes to the specificity in protein-DNA interaction is the DNA conformational change. Electrostatic neutralization of the phosphate groups by the positively charged amino acid residues in proteins is thought to bring about such conformational changes in DNA. Here, we employ molecular dynamics simulations to examine the effect of charge on amino acids Lys113, Arg145, and Asp91 which are attached to the scissile phosphate on the conformation of DNA in EcoRI-DNA complex. The results indicate that the charge of these amino acids is essential for maintaining the local conformation of DNA in the EcoRI-bound form. Interestingly, we observe that the positively charged amino acids Lys113 and Arg145 have a long-range influence on the DNA conformation, whereas the negatively charged amino acid Asp91 has only a localized effect on the DNA conformation. The charge on the amino acids also alters the collective dynamics of EcoRI. Collectively, the results shed light on the diversity of the effect of charges on DNA conformation as well as on protein dynamics.
authors.affiliation: a School of Chemical and Biotechnology , SASTRA University , Thanjavur 613401 , India.
authors.forename: Sreelakshmi
authors.initials: S
authors.lastname: Ramachandrakurup
authors.affiliation: a School of Chemical and Biotechnology , SASTRA University , Thanjavur 613401 , India.
authors.forename: Sumanth
authors.initials: S
authors.lastname: Ammapalli
authors.affiliation: a School of Chemical and Biotechnology , SASTRA University , Thanjavur 613401 , India.
authors.forename: Vigneshwar
authors.initials: V
authors.lastname: Ramakrishnan
mesh_terms: D020816:Amino Acid Motifs; D001120:Arginine / Q000737:chemistry*; D001224:Aspartic Acid / Q000737:chemistry*; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D015246:Deoxyribonuclease EcoRI / Q000737:chemistry*; D004926:Escherichia coli / Q000737:chemistry*; D006860:Hydrogen Bonding; D007700:Kinetics; D008239:Lysine / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D001224:Aspartic Acid; D004247:DNA; D001120:Arginine; D015246:Deoxyribonuclease EcoRI; D008239:Lysine
keywords: DNA kinks; essential dynamics; inner product matrix; molecular dynamics; partial neutralization