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Spatholobus parviflorus seed lectin (SPL) is a heterotetrameric lectin, with two α and two β monomers. In the crystal structure of SPL α monomer, two residues at positions 240 and 241 are missing. This region was modeled based on the positional and sequence similarities. The role of metal ions in SPL structure was analyzed by 10 ns molecular dynamics simulation. MD simulations were performed in the presence and absence of metal ions to explain the loss of haemagglutinating property of the lectin due to demetallization. Demetallized structure was found to deviate drastically at the metal binding loop region. Affinity of different sugars like N-acetyl galactosamine (GalNAc), D-galactose and lactose towards the native and demetallized protein was calculated by molecular docking studies. It was found that the sugar binding site got severely distorted in demetallized lectin. Consequently, sugar binding ability of lectin might be decreasing in the demetallized condition. Isothermal titration calorimetric (ITC) analysis of the sugars in the presence of native and demetallized protein confirmed the in silico results. It was observed after molecular dynamics simulations, that significant structural deviations were not caused in the quaternary structure of demetallized lectin. It was confirmed that the structural changes modified the sugar binding ability, as well as sugar specificity of the present lectin. The role of metal ions in sugar binding is described based on the in silico studies and ITC analysis. A comprehensive analysis of the ITC data suggests that the sugar specificity of the metal bound lectin and the loss of sugar specificity due to metal chelation are not linear.

Phospholipase A2 (PLA₂) is one of the key enzymes involved in the formation of inflammatory mediators. Inhibition of PLA₂ is considered to be one of the efficient methods to control inflammation. In silico docking studies of 160 selected indole derivatives performed against porcine pancreatic PLA₂ (ppsPLA2) suggested that, CID2324681, CID8617 (indolebutyric acid or IBA), CID22097771 and CID802 (indoleacetic acid or IAA) exhibited highest binding energies. In silico analysis was carried out to predict some of the ADME properties. The binding potential of these compounds with human non pancreatic secretory PLA₂ (hnpsPLA₂) was determined using molecular docking studies. In order to corroborate the in silico results, enzyme kinetics and isothermal titration calorimetric analysis of the two selected compounds, IAA and IBA were performed against ppsPLA₂. From the analysis, it was concluded that IAA and IBA can act as competitive inhibitors to the enzyme and may be used as anti inflammatory agents.

Acetylcholinesterase (AChE) inhibitors are currently in focus for the pharmacotherapy of Alzheimer's disease (AD). These inhibitors increase the level of acetylcholine in the brain and facilitate cholinergic neurotransmission. AChE inhibitors such as rivastigmine, galantamine, physostigmine and huperzine are obtained from plants, indicating that plants can serve as a potential source for novel AChE inhibitors. We have performed a virtual screening of diverse natural products with distinct chemical structure against AChE. NDGA was one among the top scored compounds and was selected for enzyme kinetic studies. The IC(50) of NDGA on AChE was 46.2 μM. However, NDGA showed very poor central nervous system (CNS) activity and blood-brain barrier (BBB) penetration. In silico structural modification on NDGA was carried out in order to obtain derivatives with better CNS activity as well as BBB penetration. The studies revealed that some of the designed compounds can be used as lead molecules for the development of drugs against AD.