Partitioning of energy in the interaction of non-intercalating antibiotics (netropsin, netropsin without its cationic ends and two analogs of distamycin A) with different base sequences of B-DNA is studied here by the atom-atom potential technique and geometry optimization procedures. The results show that electrostatic forces contribute substantially to the stabilization energy as well as to the sequence specificity. The hydrogen-bonding term is also sequence specific and is significant in properly orienting the drug molecule. Relative roles of the hydrogen bonding and electrostatic interactions depend on the dielectric property of the medium.

We present models for the interaction of glucocorticoids: dexamethasone (DEX), dexamethasone-21-mesylate (DEXM) and deacylcortivazol (DAC) with the hexanucleotide sequence d(TGTTCT), (CORE sequence) found in the long terminal repeat of MMTV. These models are obtained by computer-aided geometry simulation with energy minimization technique, making use of the empirical potential energy functions. We have considered both intercalative A d nonintercalative binding. Differences in the glucocorticoid activity of these steroids are explained on the basis of stereochemical and energetic differences. A model is proposed for interaction of the steroid-receptor complex with the hormone-responsive element (HRE).

Geometry of the complex of a steroid hormone, dexamethasone, with a hexanucleotide sequence from the glucocorticoid responsive element d(TGTTCT)z, is optimised here using computer aided geometry simulation with an energy minimization technique. We have also optimised its geometries with genetically modified and arbitrarily chosen DNA sequences. The drug molecule is considered to have both intercalative as well as non-intercalative binding. Comparison of energetics and stereochemical aspects, as well as the H-bonding scheme, is used here to bring out salient features about the mechanism of DNA sequence recognition by steroid hormones.

Computer model building with a dynamic energy minimization procedure is used here to study the interaction of a pentapeptide sequence from the lac repressor headpiece (lac 53-57) with different base sequences of DNA. The peptide fragment for this purpose was considered in the classical j?-antiparallel as well as the P-associated conformation. The model of its interaction with DNA was optimised for various binding positions and base sequences. Partitioning of energy is analysed for different dielectric constant values and the main contributing factors to sequence-specific binding are discussed. DNA recognition lac 53-5 7 Energy partitioning

A heptanucleotide sequence d(TATCACC)2 from OR3 region of bacteriophage lambda is considered sufficient for the recognition of Cro protein. We present here results on molecular dynamic simulations on this sequence for 100 ps in 0.02 ps interval. The simulations are done using computer program GROMOS. The conformational results are averaged over each ps. The IUPAC torsional parameters for 100 conformations are illustrated using a wheal and a dial systems. Several other stereochemical parameters such as H-bonding lengths and angles, sugar puckers, helix twist and roll angles as also distances between opposite strand phosphorus are depicted graphically. We find that there is rupture of terminal H-bonds. The bases are tilted and shifted away from the helix axis giving rise to bifurcated H-bonds. H-bonds are seen even in between different base pairs. The role of these dynamic structural changes in the recognition of OR3 operator by Cro protein is discussed in the paper.