PROTEIN-NUCLEIC ACID INTERACTIONS : INTERACTION OF TYROSINE CONTAINING MODEL OLIGOPEPTIDES WITH SOME DEOXYOLIGONUCLEOTIDES

Abstract

There has been a great interest in the precise determination of structure of DNA molecules of varying sequence and of their complexes with protein molecules. But these biological systems are very complex. So model systems have been extensively used. The obvious advantage is the possibility to investigate interactions of DNA-peptide system with controlled amino acid composition, sequence, chain lengths and predictable conformation which results in considerable simplification of the system as compared to the natural DNA-protein systems. The present work is on a functional part of DNA binding lo of Gene V Protein comprising of residues, Lys -Pro-Tyr-Ser-Leu-Asn**. We have studied interaction of this synthetic peptide with a single-stranded d(A) and double-stranded DNA (d-GACTCGTC) by NMR techniques. One dimensional NMR, 2D COSY and NOESY spectra are used to get changes in chemical shift, T*., spin-spin couplings, interproton distances, intermolecular NOEs and hence the structural details. The results establish a role of Tyr, Lys, Pro, and Leu residues. We also present results obtained by theoretical calculations using classical potential functions on the stacking of nucleic acid bases (A,T,G,C) and base-pairs (AT,CG) with aromatic amino acids. Intercalation of aromatic amino acids between model dinucleotide systems such as d-CG, d-CC, d-AT, d-AA have been studied. Unwinding and winding of DNA helix upon intercalation have been investigated. Conformational energy of complexes of amino acids with single- stranded DNA have also been computed. Overlap geometries in the optimised conformations have been obtained. The trends in interaction energy suggest that Trp and His are involved in the formation of more stable complex than Tyr and Phe. Among dinucleotide model systems, homonucleotides show strong binding to aromatic amino acids. The molecular op mechanisms involved in these interactions show a specificity in protein-nucleic acid associations.