Molecular characterization of chilli leaf curl Ahmedabad virus: homology modelling and evaluation of viral proteins interacting with host protein SnRK1 and docking against flavonoids-an in silico approach.

Chilli leaf curl Ahmedabad virus (ChiLCAV), a begomovirus belonging to the family Geminiviridae, has been reported for its occurrence in India, infecting chilli and tomato plants. The viral proteins associated with ChiLCAV involves in the primary pathogenesis and transmission of the virus by whitefly. Viral protein interactions with host proteins show the dynamics of structural binding and interaction in their infection cycle. At the same time, plants have multiple defence mechanisms against bacterial and viral infections. Secondary metabolites play a significant role in the inborne defence mechanism of plants. Host proteins are also the prime producers of secondary metabolites. In the present study, we evaluated the host protein SnRK1 interaction with all six viral proteins (V1, V2, C1, C2, C3 and C4). Apart from C4, all the other viral proteins showed appreciable binding and interaction with SnRK1. SnRK1 has the regulation mechanism for the accumulation of diterpenoids, secondary metabolites. Flavonoids are secondary metabolites produced by the plant under stress conditions. Further, we studied the binding and interaction of six selected flavonoids produced by Solanaceae family members with all the ChiLCAV proteins. All six selected flavonoids showed considerable binding energy with all viral proteins. Each flavonoid showed high binding energy with different viral proteins. Molecular docking is carried out for both flavonoids and the host protein SnRK1. These in silico interactions and docking studies could be useful for understanding the plants defence mechanism against viral infections at the molecular level.

Understanding the influence of lipid bilayers and ligand molecules in determining the conformational dynamics of somatostatin receptor 2.

Somatostatin receptor 2 (SSTR2) is a G-protein coupled receptor (GPCR) that controls numerous cellular processes including cell-to-cell signaling. In this study, we report how the lipid and ligand molecules influence the conformational dynamics of the membrane-bound SSTR2. Molecular simulations of different holo and apoenzyme complexes of SSTR2 in the presence and absence of a lipid bilayer were performed, observed, and correlated with previously reported studies. We identified the important SSTR2 residues that take part in the formation of the SSTR2-ligand complex. On analyzing the molecular simulation trajectories, we identified that the residue D3.32 is crucial in determining the bioactive conformation of SSTR2 ligands in the binding site. Based on the results, we suggest that designing a novel SSTR2 ligand with an H-bond donor group at the R1 position, and hydrophobic groups at R2 and R3 might have higher activity and SSTR2-selectivity. We analyzed the simulated systems to identify other important structural features involved in SSTR2-ligand binding and to observe the different conformational changes that occur in the protein after the ligand binding. Additionally, we studied the conformational dynamics of N- and C-terminal regions of SSTR2 in the presence and absence of the lipid bilayer. Both the systems were compared to understand the influence of lipid molecules in the formation of secondary structural domains by these extracellular regions. The comparative study revealed that the secondary structural elements formed by C-terminal residues in presence of lipid molecules is crucial for the functioning of SSTR2. Our study results highlight the structural complexities involved in the functioning of SSTR upon binding with the ligands in the presence and absence of lipid bilayer, which is essential for designing novel drug targets.