Nitin Sapre

• Ph.D.
• Computational Chemist at Freelance

The paper presents in silico mutational research on the energetics of the most resolved protein structure of HIV-1 NNRTIs, the 4G1Q HIV-1 reverse transcriptase protein. Twenty nearby residues that are less than 6 Å from the center of the embedded ligand are subjected to in silico alterations. For the current study, 380 unique proteins are generated...

The paper presents the incorporation of in silico missenses and studies the effect of missenses to understand its effect on the ligand–protein interactions, of COVID-19 protein. In silico protein–ligand interaction, studies are being used to understand and investigate the drug-likeness of various molecules. 19 novel COVID-19 proteins are designed b...

The present study deals with the application of Electrotopological state (E-State) indices in identifying structural attributes, responsible for exhibiting better antiviral activity for the NNRTI class of the HEPT derivatives. Special thrust is given on the potential of using these simple 2D QSAR models in prefiltering a large chemical database. Th...

The work presents in silico mutational studies on the energetics of HIV-1 reverse transcriptase protein 4G1Q, the highest resolved protein structure of NNRTIs of HIV-1. In silico mutations are induced on the twenty neighbouring residues, surrounding the embedded ligand, within the vicinity of 6 Å from the centre of the ligand. These 20 surrounding...

The paper presents the incorporation of in silico missenses and studies the effect of missenses to understand its effect on the Ligand-Protein interactions, of COVID-19 protein. In silico protein-ligand interaction, studies are being used to understand and investigate the drug-likeness of various molecules. 19 novel COVID-19 proteins are designed b...

Design of Seven novel lead compounds, acting as NNRTIs of HIV-1. Functional group based computational molecular modelling techniques are used for such design of Acylthiocarbamate derivatives. Effect of structural characteristics on the antiviral activity of these derivatives has also been studied. Statistical regression techniques namely, Non-linea...

A GIAN course on Computational Chemistry and Computer Aided Drug Design is scheduled for April 15-19, 2019. The course will be held in The Department of Applied Chemistry, SGSITS, Indore. For Details visit: http://www.gian.iitkgp.ac.in/ccourses/approvecourses2 For Registration visit: http://www.gian.iitkgp.ac.in/GREGN/index

Six novel non-nucleoside reverse transcriptase inhibitors exhibiting high efficacy are designed using in silico mathematical modelling techniques and the results are validated using a docking technique. An in silico assessment of interaction potential and structural requirements of 5-alkyl-2-alkylamino-6-(2,6-difluorophenylalkyl)-3,4-dihydropyrimid...

Researchers are on the constant lookout for new antiviral agents for the treatment of AIDS. In the present work, ligand based modeling studies are performed on analogues of substituted phenyl-thio-thymines, which act as non-nucleoside reverse transcriptase inhibitors (NNRTIs) and novel leads are extracted. Using alignment-dependent descriptors, bas...

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have shown a lot of promise, yet their use has been limited in treating HIV-1 infection. In order to improve low treatment success rates, owing to the resistance developed, cross-resistance derived from mutational changes and fatal side-effects, modified and novel NNRTIs with better pharmacok...

The modern drug discovery has entered a realm wherein artificial intelligence plays a pivotal role in handling the huge overflow of the data and extracting vital information related to structure-activity/property relationships and rational drug design. In this communication, we present an overview of applications of Artificial Neural Networks (ANN)...

Current challenges in drug designing and lead optimization has reached a bottle neck where the main onus lies on rigorous validation to afford robust and predictive models. In the present study, we have suggested that predictive structure-activity relationship (SAR) models based on robust statistical analyses can serve as effective screening tools...

TIBO (Tetrahydroimidazo-[4,5,1-jk][1,4]-benzodiazepinone) compounds are potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) that show a great promise for the treatment of AIDS. A structure-based molecular modeling approach based on template-based flexible docking simulation followed by ‘Tabu clustering’ was performed on a series of 46 T...

Quantitative structure-activity relationships (QSAR), based on E-state indices have been developed for a series of tetrahydroimidazo-[4,5,1-jk]-benzodiazepinone derivatives against HIV-1 reverse transcriptase (HIV-1 RT). Statistical modeling using multiple linear regression technique in predicting the anti-HIV activity yielded a good correlation fo...

A template-based flexible docking simulation followed by ‘Tabu-clustering’ was performed on a series of 38 TIBO derivatives as HIV-1 reverse transcriptase (HIV-1 RT) inhibitors. Four different templates of the Cl-TIBO (1-REV) were created and used as reference templates for docking and aligning. On the basis of the optimal conformation of the ligan...

Motivation The application of Kier-Hall electrotopological state (E-state) indices has helped in deriving mathematical models, where the electronic attributes of an atom in a chemical graph could be encoded as an index. By changing a substituent in a molecule, a corresponding change in its E-state value as well as physicochemical/biological propert...

At present, chemotherapy seems to be the main weapon in the arsenal of remedies for the ongoing crusade against AIDS. The mode of binding of the TIBO family of inhibitors has been of interest because these compounds do not fit the two-hinged-ring model as generally observed in the NNRTIs. Flexible docking simulations were performed with a series of...

Lipophilicity or hydrophobicity is a crucial physico-chemical property of an oral drug compound. In the present study, we have analysed the structural parameters responsible for enhancing the lipophilicity expressed in terms of Octanol-Water partition coefficient, log P, of 2-amino-6-arylsulfonylbenzonitrile (AASBN) derivatives used as NNRTIs in AI...

In this study we have investigated the relative correlation potential of Wiener (W), Randic (χ), Balaban (J) and Szeged (Sz) indices in developing quantitative structure-activity relationships QSAR; log(1/IC50) values of 2-amino-6-arylsulfonylbenzonitrile analogues are used for this purpose. The statistical analyses for univaraite and multivariate...

A comparative study of genetic function approximation (GFA) and multiple linear regression analysis(MLR) techniques for understanding 2D quantitative structure-activity relationship (2D-QSAR) on N-methyl-D-aspartate (NMDA) inhibitors was conducted using distance and connectivity based topological indices (Wiener, Balaban and Randic Indices). Models...

Several quantitative structure-property relationships (QSPR) using the Szeged (Sz) and Wiener (W) topological indices are proposed for predicting physico-chemical properties of a series of salicylhydroxamic acid derivatives. The molecular properties used are molar refraction (MR), parachor (PR), polarizability (α) and logarithmic partition coeffici...

A novel method for the study of inhibition of DNA synthesis by hydroxyurea(s) using topological indices and frontier molecular orbital energies: Eum.MI, £lumo and KMUl is described. The data suggest that the inhibitory activities of urea(s) can be successfully modelled by these molecular descriptors. Excellent results are obtained in rnultivariate...

The Balaban index (J) has been used for proposing a series of quantitative structure-property relation (QSPR) models, which can be used for estimating physical properties of nuclear substituted salicylhydroxamic acids (SHA-derivatives). The physical properties of SHA-derivatives used are logarithm of partition coefficient (lgP), molar refraction (M...

A novel method is described for the estimation of g-tensors of some copper(II) chelates using Wiener index (W). The ESR parameters for copper(II) chelates of some hydrazones and thiosemicarbazones have been used for the purpose. The regression analysis of the data using the method of least squares indicates that W can be used for estimating g 1+ g...

In this study we have investigated the relative correlation potential of Wiener (W), Szeged (Sz), and molecular connectivity indices (0chiR, 1chiR and 2chiR) in developing quantitative structure-activity relationships, QSAR; log P values of benzoic acid and its nuclear-substituted derivatives were used for this purpose. The statistical analyses for...

A novel method for the study of inhibition of DNA synthesis by hydroxyurea(s) using topological indices and frontier molecular orbital energies:E homo,E lumo andE total is described. The data suggest that the inhibitory activities of urea(s) can be successfully modelled by these molecular descriptors. Excellent results are obtained in multivariate...

In alkanes, the Wiener (W), Schultz (MTI) and Szeged (Sz) topological indices are known to be closely related, being thus equally capable of predicting the physico-chemical properties of these compounds. We have now examined cycloalkanes and found that for them: (a) W, MTI and Sz are linerly correlated, (b) the correlations of W, MTI and Sz with bo...

Weight loss experiments for the copper(II) chelate of salicylhydrazide (Cu(II)-SH) were followed by thermogravimetry (TG). The curves were analysed by the Horowitz-Metzger and Coats-Redfern methods. Refined values of the kinetic and thermodynamic variables were obtained by regression analysis. The kinetic variables for the thermal dehydration estim...

The thermal dehydration of Tl(MAL) · 3H2O, where MAL stands for the anion of malic acid and Tl for thallium in the trivalent state, was studied by thermogravimetric (TG), differential thermogravimetric (DTG) and differential thermal analysis (DTA) techniques. The results show the release of all three water molecules in a single step, indicating the...