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Biomedical subjects

V Kothekar

Publications and source records attributed to V Kothekar.

At least 37 records · Page 2Linked to original sources
PubMed1991

100ps molecular dynamic simulation of d(TATCACC)2.

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.

Bacteriophage lambda↗
PubMed1990

Computer simulation of zinc finger motifs from cellular nucleic acid binding protein and their interaction with consensus DNA sequences.

We report here a computer simulation of the three-dimensional structures of seven zinc finger motifs from cellular nucleic acid binding protein involved in negative feedback inhibition of cholesterol biosynthesis. The structures are optimised using steric constraints imposed by tetrahedral coordination of the zinc ion with Cys and His residues, by molecular mechanics technique. We have also optimised the structure of a finger-I with GpT sequence. The model for the interaction of seven fingered protein with single-stranded d(GTGCGGTG) from sterol regulatory element (SRE) is given on the basis of these results. We also propose a scheme for recognition of a multifingered regulatory protein with small single-stranded DNA fragments.

Amino Acid Sequence↗
PubMed1987

On the possible mechanism of recognition of DNA base sequence by steroid hormones.

Geometry of the complex of a steroid hormone, dexamethasone, with a hexanucleotide sequence from the glucocorticoid responsive element d(TGTTCT)2, 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.

Base Sequence↗
PubMed1987

Theoretical study on binding of Hoechst 33258 with oligonucleotides.

Computer modelling with an energy minimization procedure is used here to obtain stereochemical and energetic details for complexes of the dye Hoechst 33258 with different oligonucleotide sequences. An optimised model of the dye with d(A)5 X d(T)5 is in conformity with previous proposed models. It has bifurcated hydrogen bonds between N2H and N4H of benzimidazole rings with N3 of adenine and O2 of thymine. Relative binding energies with different oligonucleotides show preference for AT containing sequences, with an intermediate affinity between that for netropsin and distamycin-2. Reduced binding is observed at high ionic concentration. The benzimidazole rings are twisted with respect to the phenol ring in the optimal model. This gives desired curvature to the molecule which is stabilised by intermolecular forces.

Benzimidazoles↗
PubMed1986

Energetics of interaction of oligopeptide (lac 53-57) with DNA base sequences and origin of sequence-specific recognition.

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 beta-antiparallel as well as the beta-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.

Base Sequence↗
PubMed1986

Origin of sequence-specific recognition of DNA by non-intercalating anti-tumor antibiotics.

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.

Antibiotics, Antineoplastic↗
PubMed1985

On the origin of sequence dependent structural changes in DNA.

Sequence specificity in the backbone conformation of DNA is controlled mostly by the electrostatic part of the base backbone interactions. However, local mobility or orientation of the bases depends on stacking and base backbone interactions. Latter has both non-bonded and electrostatic components. Environmental factors manifest themselves essentially through the electrostatic part of base-backbone interactions. They affect both backbone as well as internal core conformation and play a great role in biological recognition.

Base Sequence↗
PubMed1983

Biophysical studies on molecular mechanisms of abortifacient action of prostaglandins. V. CNDO/2 estimation of the relative affinities of the cations Na+, Mg2+ and Ca2+ to the carboxylic group.

The paper describes the study of relative affinities of the cations Na+, Mg2+ and Ca2+ to the carboxylic group, their electronic structure and optimum binding positions on the basis of the CNDO/2 technique, using the well known supramolecular approach. The cation for this purpose was made to approach the carboxylic group in various possible directions in and out of the plane C1O1AO1B and the final parameters were evaluated for the optimum planar as well as nonplanar geometries. With the exception of Ca2+ the nonplanar geometries were always favoured over the planar ones for binding at O1A and O1B, whereas for symmetric binding between O1A and O1B planar geometries were favoured for Mg2+ and Ca2+. The distance between the cation and oxygen was slightly larger for this geometry and Etot which followed the order Mg2+ less than Ca2+ less than Na+ had the lowest value.

Abortifacient Agents↗
PubMed1983

Biophysical studies on molecular mechanism of abortifacient action of prostaglandins. VI. Conformation energy calculation on PGE2, PGF2 alpha and 15-(s)-methyl PGF2 alpha.

This paper reports the conformation energy (CE) calculations on PGE2, PGE2 alpha and 15-(s)-methyl PGE2 alpha on the basis of empirical potential energy functions for the simultaneous rotations around C7-C8 (psi), C12-C13 (theta) and C14-C15 (phi) bonds. The variation of the minimum conformation energy E for each isoenergy map in the psi theta plane with respect to phi gives two minima around 90 degrees and 240 degrees in PGE2, 60 degrees and 245 degrees in PGF2 alpha, and 60 degrees and 150 degrees in 15-(s)-methyl PGF2 alpha. The latter two forms also have a small dip at 270 degrees. The pattern of allowed low energy conformations of PGF2 alpha and 15-(s)-methyl PGF2 alpha is quite similar and is characterized by the existence of six low energy regions.

Abortifacient Agents↗