Potential Acetylcholinesterase Inhibitor Acting on the Pesticide Resistant and Susceptible Cotton Pests.

Gossypium spp., produces economically important cotton fiber, and its yield is highly affected due to pest attacks. Insecticidal target site mutation is one of the reasons behind insecticide resistance to a wide range of pesticides. Acetylcholinesterase (AChE) protein sequences from major pests of cotton were analyzed to assess various physicochemical properties, presence of motifs, and understand evolutionary relationship. The impact of three mutant AChE1, A. lucorum A216S, B. tabaci F392W, and A. gossypii A302S, on the strucutral stability was assessed, and F392W_AChE1 was selected based on 100 ns molecular dynamics simulation. Virtual screening of the zinc database and high-throughput virtual screening, standard precision, and extra precision docking resulted in the identification of six compounds. The six identified compounds and six known commercial pesticdes were docked with three mutant and three wild type AChE1, and one (C1) was selected based on Tice criteria. The conformational and interaction stability of the AChE1-C1 and F392W_AChE1-C1 complexes were monitored at 100 ns Gromacs simulation and were found to be thermodynamically favorable. Therefore, C1 may have the potential to bind to the resistant and susceptible strains of cotton pest, and the resistance developed by insects could be arrested. Furthermore, synthesis and field study of C1 will lead us to a better understanding of the efficacy of the identified compound.

Screening of broad spectrum natural pesticides against conserved target arginine kinase in cotton pests by molecular modeling.

Cotton is an economically important crop and its production is challenged by the diversity of pests and related insecticide resistance. Identification of the conserved target across the cotton pest will help to design broad spectrum insecticide. In this study, we have identified conserved sequences by Expressed Sequence Tag profiling from three cotton pests namely Aphis gossypii, Helicoverpa armigera, and Spodoptera exigua. One target protein arginine kinase having a key role in insect physiology and energy metabolism was studied further using homology modeling, virtual screening, molecular docking, and molecular dynamics simulation to identify potential biopesticide compounds from the Zinc natural database. We have identified four compounds having excellent inhibitor potential against the identified broad spectrum target which are highly specific to invertebrates.

Insights from the Molecular Modelling and Docking Analysis of AIF-NLS complex to infer Nuclear Translocation of the Protein.

Apoptosis Inducing Factor protein has a dual role depending on its localization in mitochondrion (energy production) and nucleus (induces apoptosis). Cell damage transports this protein to nucleus which otherwise favors mitochondrion. The alteration of Nuclear Localisation Signal tags could aid nuclear translocation. In this study, apoptosis inducing factor protein (AIF) was conjugated with strong NLS tags and its binding affinity with Importin was studied using in silico approaches such as molecular modeling and docking. This aims to improve the docking affinity of the AIF-Importin complex thus allowing for nuclear translocation, in order to induce caspase-independent apoptosis of the cell.

Combined pharmacophore, virtual screening and molecular dynamics studies to identify Bruton's tyrosine kinase inhibitors.

Bruton's tyrosine Kinase (BTK) is a cytoplasmic, non-receptor tyrosine kinase expressed in hematopoietic cells. BTK plays a critical role in many cellular signalling pathways making it a potential target to treat autoimmune diseases and cancer. BTK signalling is important for the production of arthritis-associated antibodies, and inhibiting BTK will help the system to block the production of disease-associated antibodies. In this study, we have implemented ligand-based pharmacophore modelling and virtual screening against natural compounds followed by molecular docking, density functional theory and molecular dynamics studies for 50 ns. Four compounds with high affinity towards BTK were identified, and it could be used as a potent lead molecule for designing BTK inhibitor.

SeeHaBITaT: A server on bioinformatics applications for Tospoviruses and other species.

Plant viruses are important limiting factors in agricultural productivity. Tospovirus is one of the severe plant pathogens, causing damage to economically important food and ornamental crops worldwide through thrips as vectors. Database application resources exclusively on this virus would help to design better control measures, which aren't available. SeeHaBITaT is a unique and exclusive web based server providing work bench to perform computational research on tospoviruses and its species. SeeHaBITaT hosts Tospoviruses specific database Togribase, MOLBIT, SRMBIT and SS with PDB. These applications would be of immense help to the Tospovirus scientific community. The server could be accessed at http://bit.srmuniv.ac.in/.

NNvPDB: Neural Network based Protein Secondary Structure Prediction with PDB Validation.

UNLABELLED: The predicted secondary structural states are not cross validated by any of the existing servers. Hence, information on the level of accuracy for every sequence is not reported by the existing servers. This was overcome by NNvPDB, which not only reported greater Q3 but also validates every prediction with the homologous PDB entries. NNvPDB is based on the concept of Neural Network, with a new and different approach of training the network every time with five PDB structures that are similar to query sequence. The average accuracy for helix is 76%, beta sheet is 71% and overall (helix, sheet and coil) is 66%. AVAILABILITY: http://bit.srmuniv.ac.in/cgi-bin/bit/cfpdb/nnsecstruct.pl.