Asian corn borer (ACB) is a destructive insect pest of corn and causes up to 80% yield reduction in the Philippines. Synthetic insecticides have been used to control ACB but they pose a risk to human health and the environment. The use of synergists increases insecticide effectiveness and decreases the frequency of insecticide application. In line with this principle, we performed in silico screening of phytochemicals from bayati against glutathione-s-transferase (GST), one of the important detoxifying enzymes of ACB. Homology modeling was done to generate an acceptable three-dimensional protein structure (OfGST). Through ensemble molecular docking, we found that three phytosterols (stigmasterol, lupeol, and gamma-sitosterol) from bayati have a higher binding affinity to OfGST than glutathione, its natural substrate. Molecular dynamics simulation revealed that lupeol and gamma-sitosterol have a greater stabilizing effect on OfGST than stigmasterol, as supported by the RMSD, radius of gyration, and SASA plots of all complexes. Communicated by Ramaswamy H. Sarma

The multifunctional enzyme cyclin-dependent kinase 2 (CDK2) protein is essential for cell proliferation, transcription and modulation of the cell cycle. There is a dysfunction that is connected to various diseases, such as cancer, making it an important treatment target in oncology and beyond. The goal of this study is to identify novel CDK2 ATP binding site inhibitors using in silico drug designing. To find competitive inhibitors for the ATP site, molecular docking, molecular dynamics (MD) simulation and free-binding energy calculations were used. Natural compounds retrieved from marine sources (fungi and algae) were docked against protein, and the best-binding compounds were further evaluated using MD simulations. LIG1, LIG2 and LIG3 (ΔG_PB = −19.98, −15.82 and −12.98 kcal/mol, respectively) were placed in the top positions based on their overall binding energy calculated using MMPBSA approach. Stability of the complexes was confirmed by carefully analyzing the rmsd and rmsf patterns retrieved from the MD trajectories. Several residues and areas (Leu124, Val123, Phe80, Leu83, Glu81, Arg 126, Asn132, Leu134, Gln131, Lys88 and Glu195) appear to be critical for inhibitor retention across the active pocket, according to RMSD and RMSF. The dynamics of the ligands inside the active pocket were mapped using principle component analysis. It has been observed that LIG1-3 appear to be the best possible inhibitors due to their high binding energies, interaction pattern and retention inside the active pocket. Communicated by Ramaswamy H. Sarma

The brown dog tick (Rhipicephalus sanguineus) is the most prevalent tick in the world and a well-recognized vector of many pathogens affecting dogs and occasionally humans. Pathogens exploit tick salivary molecules for their survival and multiplication in the vector and transmission to and establishment in the hosts. Tick saliva contains various non-proteinaceous substances and secreted proteins that are differentially produced during feeding and comprise of inhibitors of blood congealing and platelet aggregation, vasodilatory and immunomodulatory substances, and compounds preventing itch and pain. One of these proteins is Evasin-1, which has a high binding affinity to certain types of chemokines. The binding of Evasin-1 to chemokines prevents the detection and immune response of the host to R. sanguineus, which may result in the successful transmission of pathogens. In this study, we screened potential Evasin-1 inhibitor based on the pharmacophore model derived from the binding site residues. Hit ligands were further screened via molecular docking and virtual ADMET prediction, which resulted in ZINC8856727 as the top ligand (binding affinity: -9.1 kcal/mol). Molecular dynamics simulation studies, coupled with MM-GBSA calculations and principal component analysis revealed that ZINC8856727 plays a vital role in the stability of Evasin-1. We recommend continuing the study by developing a formulation that serves as a potential medicine aid immune response during R. sanguineus infestation.

The corn planthopper, Peregrinus maidis Ashmead (Hemiptera:Delphacidae), is a widely distributed insect pest which serves as a vector of two phytopathogenic viruses, Maize mosaic virus (MMV) and Maize stripe virus (MStV). It transmits the viruses in a persistent and propagative manner. MMV is an alphanucleorhabdovirus with a negative-sense, single-stranded RNA unsegmented genome. One identified insect vector protein that may serve as receptor to MMV is Syntaxin-18 (PmStx18) which belongs to the SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) proteins. SNAREs play major roles in the final stage of docking and subsequent fusion of diverse vesicle-mediated transport events. In this work, in silico analysis of the interaction of MMV glycoprotein (MMV G) and PmStx18 was performed. Various freely available protein-protein docking web servers were used to predict the 3 D complex of MMV G and PmStx18. Analysis and protein-protein interaction (PPI) count showed that the complex predicted by the ZDOCK server has the highest number of interaction and highest affinity, as suggested by the calculated solvation free energy gain upon formation of the interface (ΔⁱG = −31 kcal/mol). Molecular dynamics simulation of the complex revealed important interactions at the interface over the course of 25 ns. This is the first in silico analysis performed for the interaction on a putative receptor of P. maidis and MMV G. The results of the PPI prediction provide novel information for studying the role of Stx18 in the transport, docking and fusion events involved in virus particle transport in the insect vector cells and its release. Communicated by Ramaswamy H. Sarma