Structure-based Assessment of Homologous Analogues of Natural products: A computational approach to predict the therapeutic effects of natural products

The present study describes a novel strategy to screen natural products (NPs) for their therapeutic effects with the predicted mechanism of action. The method entitled 'Structure-based Assessment of Homologous Analogues of Natural products-SAHANA' follows the comparison of NPs against prescribed synthetic chemical drugs to deduce activity cliffs and core fragments, based on the molecular properties and 2-dimensional structural similarities. The method was applied to predict the biological effect of the identified NPs as antidiabetic molecules. Selected NPs were assessed for their pharmacokinetic and pharmacodynamics properties. The biological interactions and structural stability of the bound structures were evaluated using molecular docking and molecular dynamics simulations. The study yielded NPs with significant structural similarities to prescribed drugs. Further, their binding interactions stabilized the macromolecular structure. The results envisage a strong indication that the natural products can produce therapeutic effects efficiently if administered individually. The results also encourage using the current screening strategy to identify competent natural product drugs against any disease condition ad libitum.