G Narahari Sastry
Articles written in Journal of Chemical Sciences
Volume 128 Issue 5 May 2016 pp 719-732 Regular Articles
Multidrug resistance in Mycobacterium tuberculosis (M. Tb) and its coexistence with HIV arethe biggest therapeutic challenges in anti-M. Tb drug discovery. The current study reports a Virtual Screening(VS) strategy to identify potential inhibitors of Mycobacterial cyclopropane synthase (CmaA1), an importantM. Tb target considering the above challenges. Five ligand-based pharmacophore models were generatedfrom 40 different conformations of the cofactors of CmaA1 taken from molecular dynamics (MD) simulationstrajectories of CmaA1. The screening abilities of these models were validated by screening 23 inhibitors and1398 non-inhibitors of CmaA1. A VS protocol was designed with four levels of screening i.e., ligand-basedpharmacophore screening, structure-based pharmacophore screening, docking and absorption, distribution,metabolism, excretion and the toxicity (ADMET) filters. In an attempt towards repurposing the existing drugsto inhibit CmaA1, 6,429 drugs reported in DrugBank were considered for screening. To find compounds thatinhibit multiple targets of M. Tb as well as HIV, we also chose 701 and 11,109 compounds showing activitybelow 1 μM range on M. Tb and HIV cell lines, respectively, collected from ChEMBL database. Thus, a totalof 18,239 compounds were screened against CmaA1, and 12 compounds were identified as potential hits forCmaA1 at the end of the fourth step. Detailed analysis of the structures revealed these compounds to interactwith key active site residues of CmaA1.
Volume 128 Issue 10 October 2016 pp 1641-1649 Regular Article
Interaction between lithium and carbonaceous materials has gained a lot of importance in lithium battery industry as an important source of energy and storage. The size, dimension, curvature and chirality of the carbonaceous materials are found to be very important factors in controlling the sequential binding oflithium. The propensity of lithium binding to the monolayer carbonaceous materials has been studied using Density functional theory (DFT). Structural and energetical parameters of the complexes have been analyzed through interaction energy, sequential energy, Mulliken population analysis and spin density distribution. Spindensity of odd Li doped systems reveals the preferences for addition of further lithium atoms on the surface. Upon analyzing the interaction energy in armchair carbon nanotubes (A-CNTs) and zigzag carbon nanotubes (Z-CNTs), it has been observed that external and internal surfaces of CNTs have contrasting binding preferences for sequential addition of Li atoms. Internal surface is found to be more feasible site for lithium adsorption than the external surface. This current study provides fundamental understanding of the mechanism of lithium adsorption in lithium battery.
Volume 129 Issue 5 May 2017 pp 515-531 Regular Article
ANAMIKA SINGH GAUR ANSHU BHARDWAJ ARUN SHARMA LIJO JOHN M RAM VIVEK NEHA TRIPATHI PRASAD V BHARATAM RAKESH KUMAR SRIDHARA JANARDHAN ABHAYSINH MORI ANIRBAN BANERJI ANDREW M LYNN ANMOL J HEMROM ANURAG PASSI APARNA SINGH ASHEESH KUMAR CHARUVAKA MUVVA CHINMAI MADHURI CHINMAYEE CHOUDHURY D ARUN KUMAR DEEPAK PANDIT DEEPAK R BHARTI DEVESH KUMAR ER AZHAGIYA SINGAM GAJENDRA PS RAGHAVA HARI SAILAJA HARISH JANGRA KAAMINI RAITHATHA KARUNAKAR TANNEERU KUMARDEEP CHAUDHARY M KARTHIKEYAN M PRASANTHI NANDAN KUMAR N YEDUKONDALU NEERAJ K RAJPUT P SRI SARANYA PANKAJ NARANG PRASUN DUTTA R VENKATA KRISHNAN REETU SHARMA R SRINITHI RUCHI MISHRA S HEMASRI SANDEEP SINGH SUBRAMANIAN VENKATESAN SURESH KUMAR UCA JALEEL VIJAY KHEDKAR YOGESH JOSHI G NARAHARI SASTRY
Molecular Property Diagnostic Suite (MPDSTB) is a web tool (http://mpds.osdd.net) designed to assist the in silico drug discovery attempts towards Mycobacterium tuberculosis (Mtb). (MPDSTB) tool has nine modules which are classified into data library (1–3), data processing (4–5) and data analysis (6–9). Module 1 is a repository of literature and related information available on the Mtb. Module 2 deals with the protein targetanalysis of the chosen disease area. Module 3 is the compound library consisting of 110.31 million unique molecules generated from public domain databases and custom designed search tools. Module 4 contains toolsfor chemical file format conversions and 2D to 3D coordinate conversions. Module 5 helps in calculating the molecular descriptors. Module 6 specifically handles QSAR model development tools using descriptors generated in the Module 5. Module 7 integrates the AutoDock Vina algorithm for docking, while module 8 provides screening filters. Module 9 provides the necessary visualization tools for both small and large molecules. The workflow-based open source web portal,(MPDSTB) 1.0.1 can be a potential enabler for scientists engaged in drug discovery in general and in anti-TB research in particular.
Volume 129 Issue 7 July 2017 pp 1053-1060 REGULAR ARTICLE
Many-body expansion (MBE) has been carried out to investigate two- to five-body energy terms and their contributions to the interaction energy (IE) of (H₂O)₁₅ cluster. We have observed that the erroneous contribution of many-body terms on IE originated from cheaper convergence thresholds set as default in popular quantum mechanics packages. The propagation of errors from smaller to higher-body terms, due to the combinatorial nature of MBE, is also observed.
Volume 133 All articles Published: 8 September 2021 Article ID 0097
Recent years have witnessed a remarkable surge in the study of noncovalent interactions andtheir role in diverse areas of chemistry, biology, material science and allied fields. Among all, hydrogenbonding is quite extensively studied. Several other noncovalent interactions continue to attract wide attention.Notably, cation-π interactions play a crucial role in the function of several binding sites, reaction mechanisms,self-assemblies, catalytic mechanisms, adhesion and cohesion properties in many biological andchemical systems. The current review focuses on the character of cation-π interactions, its range and itsoccurrence from a conceptual point of view. The range and nature of cation-π interactions depend on the typeof π-system and cation involved, besides solvent and environment. The size and polarizability of the psystemsand the effective nuclear charge on cation and its multiplicity and spin dictate the structural andenergetic aspects of cation-π interaction. Further, factors affecting the modulation of strength and nature arebrought out in the review. The interplay between the cation-π interaction and the other noncovalent interactions,solvent and counter-ion effects are analysed, and the cooperativity of these forces in organizingsupramolecular architectures are discussed.
How strong is cation-π interaction depends on various factors: It may be weak, medium or strong depending on the nature of cation, π system and environment. The strength of the interaction was shown to alternate a few orders of magnitude depending on the environment.
Volume 134 All articles Published: 22 April 2022 Article ID 0057 Regular Article
Exploring the new therapeutic indications of known drugs for treating COVID-19, popularly known as drug repurposing, is emerging as a pragmatic approach especially owing to the mounting pressure to control the pandemic. Targeting multiple targets with a single drug by employing drug repurposing known as the polypharmacology approach may be an optimised strategy for the development of effective therapeutics. In this study, virtual screening has been carried out on seven popular SARS-CoV-2 targets (3CLpro,PLpro, RdRp (NSP12), NSP13, NSP14, NSP15, and NSP16). A total of 4015 approved drugs were screened against these targets. Four drugs namely venetoclax, tirilazad, acetyldigitoxin, and ledipasvir have been selected based on the docking score, ability to interact with four or more targets and having a reasonably good number of interactions with key residues in the targets. The MD simulations and MM-PBSA studies showed reasonable stability of protein-drug complexes and sustainability of key interactions between the drugs with their respective targets throughout the course of MD simulations. The identified four drug molecules were also compared with the known drugs namely elbasvir and nafamostat. While the study has provided a detailed account of the chosen protein-drug complexes, it has explored the nature of seven important targets of SARSCoV-2 by evaluating the protein-drug complexation process in great detail.
Drug repurposing strategy against SARS-CoV2 drug targets. Computational analysis was performed to identify repurposable approved drug candidates against SARS-CoV2 using approaches such as virtual screening, molecular dynamics simulation and MM-PBSA calculations. Four drugs namely venetoclax, tirilazad, acetyldigitoxin, and ledipasvir have been selected as potential candidates.
Volume 134 All articles Published: 23 November 2022 Article ID 0114
Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic paramyxovirus which belongs to Henipavirus family, causes severe respiratory disease, and may lead to fatal encephalitis infections inhumans. NiV and HeV glycoproteins (G) bind to the highly conserved human ephrin-B2 and B3 (EFNB2 &EFNB3) cell surface proteins to mediate the viral entry. In this study, various molecular modelling approaches were employed to understand protein-protein interaction (PPI) of NiV and HeV glycoprotein(84% sequence similarity) with Human EFN (B2 and B3) to investigate the molecular mechanism ofinteraction at atomic level. Our computational study emphasized the PPI profile of both the viral glycoproteins with EFN (B2 and B3) in terms of non-bonded contacts, H-bonds, salt bridges, and identification ofinterface hotspot residues which play a critical role in the formation of complexes that mediate viral fusionand entry into the host cell. According to the reports, EFNB2 is considered to be more actively involved in the attachment with the NiV and HeV glycoprotein; interestingly the current computational study has displayed more conformational stability in HeV/NiV glycoprotein with EFNB2 complex with relatively high binding energy as compared to EFNB3. During the MD simulation, the number of H-bond formations was observed tobe less in the case of EFNB3 complexes, which may be the possible reason for less conformational stability inthe EFNB3 complexes. The current detailed interaction study on the PPI may put a path forward in designing peptide inhibitors to obstruct the interaction of viral glycoproteins with host proteins, thereby inhibiting viralentry.
The viral attachment and fusion of Nipah and Hendra virus was explored through the interaction between viral glycoprotein and the host cell surface ephrin protein. The MD simulation results displayed more stability in Nipah and Hendra glycoprotein with EFNB2 as compared to EFNB3. The residue Glu533 in the central cavity of HeV/NiV glycoprotein protein identified as the potential hotspot in binding with the G-H loop of EFNB2.
Volume 135, 2023
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