Drug repurposing is a method to identify novel therapeutic agents from the existing drugs and clinical compounds. In the present comprehensive work, molecular docking, virtual screening and dynamics simulations were carried out for ten cancer types viz breast, colon, central nervous system, leukaemia, melanoma, ovarian, prostate, renal and lung (non-small and small cell) against validated eighteen kinase targets. The study aims to understand the action of chemotherapy drugs mechanism through binding interactions against selected targets via comparative docking simulations with the state-art molecular modelling suits such as MOE, Cresset–Flare, AutoDock Vina, GOLD and GLIDE. Chemotherapeutic drugs (n = 112) were shortlisted from standard drug databases with appropriate chemoinformatic filters. Based on docking studies it was revealed that leucovorin, nilotinib, ellence, thalomid and carfilzomib drugs possessed potential against other cancer targets. A library was built to enumerate novel molecules based on the scaffold and functional groups extracted from known drugs and clinical compounds. Twenty novel molecules were prioritised further based on drug-like attributes. These were cross docked against 1MQ4 Aurora-A Protein Kinase for prostate cancer and 4UYA Mitogen-activated protein kinase for renal cancer. All docking programs yielded similar results but interestingly AutoDock Vina yielded the lowest RMSD with the native ligand. To further validate the final docking results at atomistic level, molecular dynamics simulations were performed to ascertain the stability of the protein–ligand complex. The study enables repurposing of drugs and lead identification by employing a host of structure and ligand based virtual screening tools and techniques. Communicated by Ramaswamy H. Sarma

Drug repurposing is a method to identify novel therapeutic agents from the existing drugs and clinical compounds. In the present comprehensive work, molecular docking, virtual screening and dynamics simulations were carried out for ten cancer types viz breast, colon, central nervous system, leukaemia, melanoma, ovarian, prostate, renal and lung (non-small and small cell) against validated eighteen kinase targets. The study aims to understand the action of chemotherapy drugs mechanism through binding interactions against selected targets via comparative docking simulations with the state-art molecular modelling suits such as MOE, Cresset–Flare, AutoDock Vina, GOLD and GLIDE. Chemotherapeutic drugs (n = 112) were shortlisted from standard drug databases with appropriate chemoinformatic filters. Based on docking studies it was revealed that leucovorin, nilotinib, ellence, thalomid and carfilzomib drugs possessed potential against other cancer targets. A library was built to enumerate novel molecules based on the scaffold and functional groups extracted from known drugs and clinical compounds. Twenty novel molecules were prioritised further based on drug-like attributes. These were cross docked against 1MQ4 Aurora-A Protein Kinase for prostate cancer and 4UYA Mitogen-activated protein kinase for renal cancer. All docking programs yielded similar results but interestingly AutoDock Vina yielded the lowest RMSD with the native ligand. To further validate the final docking results at atomistic level, molecular dynamics simulations were performed to ascertain the stability of the protein–ligand complex. The study enables repurposing of drugs and lead identification by employing a host of structure and ligand based virtual screening tools and techniques. Communicated by Ramaswamy H. Sarma

The key objective of the present study is to estimate the surface displacement and to understand/monitor the active deformation pattern in the Kachchh region post the 2001 Bhuj Earthquake by implementing the Persistent Scatterer Interferometric Synthetic Aperture Radar (PSI) and Differential Interferometric Synthetic Aperture Radar (DInSAR) techniques. We employed the ENVISAT ASAR (15 images), ALOS PALSAR (6 pairs) and SENTINEL-1A (117 images) data sets acquired during the periods 2003–2005, 2007–2009, and 2016–2020 respectively. The PSI results of the Envisat dataset reveals that the Kachchh mainland region has undergone an average surface deformation of ± 22 mm/yr during 2003–2005. The maximum displacement observed from the ALOS PALSAR data sets (Window-1 to 6) during the period 2007–2009 is ∼ ± 1.2 cm. Further, the ground displacement observed from the Sentinel-1A dataset during the period 2016–2020 is ±16 mm/yr for the west-central region and 6 mm/yr uplift and 8 mm/yr subsidence in the eastern Kachchh mainland region. Surprisingly, high rate of deformation is detected towards the Pachham Island, Banni, Rann and the eastern region of the Kachchh after the 2001 Bhuj event. Correlating the results of different data sets, it is concluded that the deformation is high near the vicinity of the fault zones indicating the tectonically active nature of the faults. From the obtained results, we infer that, post the 2001 Bhuj earthquake, the surface displacement in the Kachchh mainland region is escalated till 2009 which is due to continuous aftershock activity and then started declining because of the ongoing seismic settlement. The acquired deformation rates are correlating well with the GPS derived displacement rates. Further, our results will assist in accurately demarcating the extent of the fault zones and also helps in precisely marking the areas undergoing active deformation, which will aid in micro zonation studies, mitigation planning and also for the preparation of an active tectonic map for the region.

The key objective of the present study is to estimate the surface displacement and to understand/monitor the active deformation pattern in the Kachchh region post the 2001 Bhuj Earthquake by implementing the Persistent Scatterer Interferometric Synthetic Aperture Radar (PSI) and Differential Interferometric Synthetic Aperture Radar (DInSAR) techniques. We employed the ENVISAT ASAR (15 images), ALOS PALSAR (6 pairs) and SENTINEL-1A (117 images) data sets acquired during the periods 2003–2005, 2007–2009, and 2016–2020 respectively. The PSI results of the Envisat dataset reveals that the Kachchh mainland region has undergone an average surface deformation of ± 22 mm/yr during 2003–2005. The maximum displacement observed from the ALOS PALSAR data sets (Window-1 to 6) during the period 2007–2009 is ∼ ± 1.2 cm. Further, the ground displacement observed from the Sentinel-1A dataset during the period 2016–2020 is ±16 mm/yr for the west-central region and 6 mm/yr uplift and 8 mm/yr subsidence in the eastern Kachchh mainland region. Surprisingly, high rate of deformation is detected towards the Pachham Island, Banni, Rann and the eastern region of the Kachchh after the 2001 Bhuj event. Correlating the results of different data sets, it is concluded that the deformation is high near the vicinity of the fault zones indicating the tectonically active nature of the faults. From the obtained results, we infer that, post the 2001 Bhuj earthquake, the surface displacement in the Kachchh mainland region is escalated till 2009 which is due to continuous aftershock activity and then started declining because of the ongoing seismic settlement. The acquired deformation rates are correlating well with the GPS derived displacement rates. Further, our results will assist in accurately demarcating the extent of the fault zones and also helps in precisely marking the areas undergoing active deformation, which will aid in micro zonation studies, mitigation planning and also for the preparation of an active tectonic map for the region.

The linking of polysaccharide in glycoconjugate vaccine with carrier protein is an imperative step to develop a strong memory response. The excessive use of similar carrier protein known to result in bystander immunity warrants an urgent need for new carrier protein. The preparation of the glycoconjugate vaccine using cyanylation chemistry is to link the active cyanate ester site of polysaccharide with the carrier protein. In the present study, transferrin binding protein-B (Tbp-B) has been explored as a new carrier protein to develop in silico pneumococcal polysaccharide serotype-5 (PnPs-5) conjugate vaccine. The homology model of Tbp-B was constructed using the Prime module and stereochemically validated using ProSA, PDBsum and ProQ. The selected model revealed a Z-score of −5.6 within the X-ray region in ProSA analysis, LGscore: 9.776, and MaxSub: 0.8 in protein quality predictor suggesting its preferred use. Loop modeling and active site analysis followed by in silico PnPs-5 activation with cyanalyting agent CDAP was docked with Tbp-B using Glide module. The complex stability of cyanate esters with Tbp-B, analyzed by molecular dynamics (MD) simulation, revealed an average RMSD of 2.49 Å for its binding to the receptor. The RMSF values of cyanate ester-1, -2, and -3 were observed to be 1.06, 1.39 and 0.79 Å, respectively. The higher RMSF of 1.39 Å of cyanate ester-2 was further found unstable which corroborates its non-binding to the protein and also incurring conformational changes to a carrier protein. Molecular simulations revealed that cyanate ester-1 and cyanate ester-3 formed stable conjugates with carrier protein Tbp-B. Communicated by Ramaswamy H. Sarma

The linking of polysaccharide in glycoconjugate vaccine with carrier protein is an imperative step to develop a strong memory response. The excessive use of similar carrier protein known to result in bystander immunity warrants an urgent need for new carrier protein. The preparation of the glycoconjugate vaccine using cyanylation chemistry is to link the active cyanate ester site of polysaccharide with the carrier protein. In the present study, transferrin binding protein-B (Tbp-B) has been explored as a new carrier protein to develop in silico pneumococcal polysaccharide serotype-5 (PnPs-5) conjugate vaccine. The homology model of Tbp-B was constructed using the Prime module and stereochemically validated using ProSA, PDBsum and ProQ. The selected model revealed a Z-score of −5.6 within the X-ray region in ProSA analysis, LGscore: 9.776, and MaxSub: 0.8 in protein quality predictor suggesting its preferred use. Loop modeling and active site analysis followed by in silico PnPs-5 activation with cyanalyting agent CDAP was docked with Tbp-B using Glide module. The complex stability of cyanate esters with Tbp-B, analyzed by molecular dynamics (MD) simulation, revealed an average RMSD of 2.49 Å for its binding to the receptor. The RMSF values of cyanate ester-1, -2, and -3 were observed to be 1.06, 1.39 and 0.79 Å, respectively. The higher RMSF of 1.39 Å of cyanate ester-2 was further found unstable which corroborates its non-binding to the protein and also incurring conformational changes to a carrier protein. Molecular simulations revealed that cyanate ester-1 and cyanate ester-3 formed stable conjugates with carrier protein Tbp-B. Communicated by Ramaswamy H. Sarma