title: Role of DNA conformation & energetic insights in Msx-1-DNA recognition as revealed by molecular dynamics studies on specific and nonspecific complexes.
abstract: In most of homeodomain-DNA complexes, glutamine or lysine is present at 50th position and interacts with 5th and 6th nucleotide of core recognition region. Molecular dynamics simulations of Msx-1-DNA complex (Q50-TG) and its variant complexes, that is specific (Q50K-CC), nonspecific (Q50-CC) having mutation in DNA and (Q50K-TG) in protein, have been carried out. Analysis of protein-DNA interactions and structure of DNA in specific and nonspecific complexes show that amino acid residues use sequence-dependent shape of DNA to interact. The binding free energies of all four complexes were analysed to define role of amino acid residue at 50th position in terms of binding strength considering the variation in DNA on stability of protein-DNA complexes. The order of stability of protein-DNA complexes shows that specific complexes are more stable than nonspecific ones. Decomposition analysis shows that N-terminal amino acid residues have been found to contribute maximally in binding free energy of protein-DNA complexes. Among specific protein-DNA complexes, K50 contributes more as compared to Q50 towards binding free energy in respective complexes. The sequence dependence of local conformation of DNA enables Q50/Q50K to make hydrogen bond with nucleotide(s) of DNA. The changes in amino acid sequence of protein are accommodated and stabilized around TAAT core region of DNA having variation in nucleotides.
authors.affiliation: a Bioinformatics Centre , CSIR-Institute of Microbial Technology , Sector 39A, Chandigarh , India.
authors.forename: Sangita
authors.initials: S
authors.lastname: Kachhap
authors.forename: Balvinder
authors.initials: B
authors.lastname: Singh
mesh_terms: D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D005973:Glutamine / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D008239:Lysine / Q000737:chemistry*; D051957:MSX1 Transcription Factor / Q000737:chemistry* / Q000235:genetics; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; D005973:Glutamine; D004247:DNA; D008239:Lysine
keywords: HTH motif; binding energy; homeodomain; protein-DNA interactions; roll angle