Computer simulation of the interaction of α3helix of λ Cro protein with DNA and origin of sequence specific recognition

The conformation of the α3 helix of Cro protein (residues 27–36) of bacteriophage λ is optimised by the damped least square minimization technique, with the steric constraint that Cα atom positions should match the crystallographic data available to date. On the basis of minimization of total interaction and conformation energy, models for complexes of this peptide sequence with heptanucleotide duplexes from native and altered OR3 operator are obtained in the major groove of Β DNA. Analysis of the energetics for 3 sequences of the DNA show that binding strength is derived mainly from the interaction of side chains of the peptide with DNA. Sequence specificity (maximum difference in binding energy for different DNA sequences) is due to hydrogen bonding interaction. A small amount of sequence specificity is derived from non-bonded interaction also. Stereochemical aspects of peptide DNA interaction and their role in DNA recognition are discussed in this paper.