Molecular dynamics simulation in solvent of the bacteriophage 434 cI repressor protein DNA binding domain amino acids (R1-69) in complex with its cognate operator (OR1) DNA sequence

We investigated protein/DNA interactions, using molecular dynamics simulati ons computed between a 10 Angstom water layer model of the 434 cI Repressor protein DNA binding domain (DBD) amino acids (R1-69) and DNA of operator(O R1) and its flanks consisting of 28 nucleotide base pairs. Hydrogen bonding interactions were monitored. In addition, van der Waals and electrostatic interaction energies were calculated. Amino acids of the 434 cI repressor D NA recognition helix 3 formed both direct and water mediated hydrogen bonds at cognate codon-anticodon nucleotide base and backbone sites within the O R1 DNA major groove halfsites and flanking regions. In addition, hydrophili c amino acids within the loop between helix 3 and helix 4 have strong elect rostatic attraction to codon-anticodon nucleotides located within the centr al nucleotides of the minor groove between the OR1 major groove halfsites T hese interactions together induced significant structural changes in the op erator DNA manifested by overtwisting of the central nucleotide base pairs and narrowing of the minor groove between the DNA major groove halfsites. F inally, these findings offer a code for site specific DNA recognition by th e 434 cI repressor protein.