Browsing by Author "Anil C. Nair"

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A computational study of the resistance of HIV-1 aspartic protease to the inhibitors ABT-538 and VX-478 and design of new analogues
(Academic Press Inc., 1998) Anil C. Nair; Stanislav Miertus; Alessandro Tossi; Domenico Romeo
Recent experimental findings with HTV-1 protease (HTV-1 PR) mutants containing variations at four residues, M461, L63P, V82T and I84V, have shown that only mutants containing the latter two exhibit cross resistance to the inhibitors ABT-538 and VX-478. The V82T and I84V modifications in fact concern residues in the active site while the other two are in the flap (M46I) and hinge (L63P) domains of the enzyme. We have modelled the M46I/L63P, V82T/I84V and M46I/L63P/V82T/I84V (4X) mutants of HIV-PR and computed their complexation energies with these two inhibitors. A good correlation was found between these complexation energies and the trend in published inhibition constants for these inhibitors. Reasons for the decrease in binding affinities with the two critical mutants (V82T/I84V and 4X) have also been elucidated in detail. Based on these findings, we have designed several analogues of ABT-538 and VX-478, some of which show a better calculated binding affinity towards both mutant and wild type PR.
A gas phase theoretical study of the hydrogen bonding properties of some androgen antagonists using molecular orbital and molecular electric field mapping methods
(Elsevier, 1996) Anil C. Nair; P.C. Mishra
A number of anilides, alkenes and an indole derivative which are known to be potent anti-androgens were studied using molecular orbital (AM1) and molecular electric field mapping (MEF) techniques. Linear correlation coefficients between the MEF values near the tertiary hydroxyl groups of these molecules and the corresponding experimentally observed hydrogen bond donating abilities (log Kα, values) were found to be satisfactory. The study illustrates the usefulness of MEF mapping in predicting the hydrogen bond donating abilities of these molecules.
Ab initio MO studies of nuclear spin-spin coupling constants in CH4, SiH4, AlH4- and GeH4 systems
(Springer-Verlag, 1994) Anil C. Nair; P. Chandra
Ab initio molecular orbital calculations of electron coupled nuclear spin-spin coupling constants are performed for CH4, SiH4, AlH4- and GeH4 systems using the SCF perturbation theory. Basis set dependence of the major contributing terms such as orbital diamagnetic, orbital paramagnetic, spin dipolar and Fermi contact terms are studied. The study also illustrates the relative importance of bond centred functions and nuclear centred polarization functions in predicting the directly bonded and geminal couplings in the systems selected. Basis sets having uncontracted core s functions and augmented with bond functions seem to predict most of these couplings fairly satisfactorily when compared to the experimental values. © 1994 Springer-Verlag.
Ab initio MO studies of nuclear spin-spin interactions in CH3F, SiH3F and CH3OH
(1995) Anil C. Nair; P. Chandra
Ab initio molecular orbital calculations of indirect nuclear spin-spin coupling constants were carried out for CH3F, SiH3F and CH3OH molecules employing the SCF perturbation theory. The basis set dependence of the four major contributing terms (orbital diamagnetic, orbital paramagnetic, spin dipolar and Fermi contact terms) are examined. The study also illustrates the importance of uncontracting the core functions and including bond functions and nuclear-centred polarization functions in the basis set. A satisfactory agreement is observed for most of the computed couplings with their experimental counterparts.
Laser light scattering studies from blood platelets and their aggregates
(Elsevier B.V., 1996) P.J. David; Anil C. Nair; V.J. Menon; D.N. Tripathi
Platelets in plasma and in buffer have been studied using the static light scattering method. It has been observed that clustering of the platelets takes place in buffer whereas a feeble ordering occurs when they are in plasma. The structure factor for the fractal aggregates in buffer have been determined using an unweighted χ2 fit of the observed scattered light intensity with the theoretically calculated intensity which assumes an exponential cut-off form for the cluster density correlation function. The fractal dimension (D(f)) and the radius of gyration (R(e)) have been obtained from the χ2 fit, assuming a gamma distribution for the polydispersity in the size of clusters. The values of D(f) and R(e) are reported to be 2.2 and 26792.0 x 10-10 m, respectively for the platelets without agonist and 2.11 and 41225.0 x 10-10 m, respectively for the same with agonist. These values are in agreement with those reported by Latimer.
Molecular electric field mapping and structure-activity relationships for some human O6-alkylguanine-DNA alkyl transferase depleting agents
(1994) Anil C. Nair; P.C. Mishra
Electric field mapping has been carried out for certain O6- and S6-substituted purine derivatives, some of which are known to have the ability to deplete the human DNA guanine O6-alkylation damage repair enzyme called O6-alkylguanine-DNA alkyltransferase (AGT). Geometries of all the molecules are optimized using the latest semiempirical method, PM3. Point charges at different atomic sites are obtained using Mulliken population analysis. There exists a reasonably good correlation between the average electric field values near the N7 atom of the guanine moiety in these molecules and the observed AGT depleting activities. It indicates involvement of the N7 site of the guanine moiety in the reaction of these molecules with AGT, in agreement with earlier suggestions. © 1994.
Study of hydrogen bonding ability of organic molecules using electrostatic potential and electric field mapping: Role of hybridization displacement charge
(1998) C. Santhosh; Anil C. Nair; P.C. Mishra
Molecular electrostatic potential (MEP) and molecular electric field (MEF) maps of certain organic compounds were studied using optimised Hybridization Displacement Charge (HDC)-corrected Löwdin charges and Mulliken charges obtained using the Modified Neglect of Diatomic Differential Overlap (MNDO) method. The MEP minimum values computed by distributing the optimised HDC-corrected Löwdin charges according to the forms of squares of the corresponding valence s Slater atomic orbitals continuously in three dimensions were found to correlate linearly with their hydrogen bond accepting and donating abilities. The average MEF values near the appropriate sites on the van der Waals surfaces of the molecules were also found to correlate linearly with their hydrogen bond accepting abilities of molecules. Further, the MEP and MEF values computed using optimised HDC-corrected Löwdin charges were found to provide much better linear correlations with the observed hydrogen bond forming abilities of the molecules than those obtained using Mulliken charges.