Background: Diabetes is the foremost health problem worldwide predisposing to increased
mortality and morbidity. The available synthetic drugs have serious side effects and thus, emphasize
further need to develop effective medication therapy. GPR40 represents an interesting target for developing
novel antidiabetic drug. In the current study, searching of potential natural hit candidate as agonist
by using structure based computational approach.
Methods: The GPR40 agonistic activity of natural compounds was searched by using Maestro through
docking and Molecular Dynamics (MD) simulation application. Virtual screening by using IBScreen
library of natural compounds was done and the binding modes of newer natural entity(s) were investigated.
Further, MD studies of the GPR40 complex with the most promising hit found in this study justified
the stability of these complexes.
Results: The silicone chip-based approach recognized the most capable six hits and the ADME prediction
aided the exploration of their pharmacokinetic potential. In this study, the obtained hit
(ZINC70692253) after the use of exhaustive screening having binding energy -107.501 kcal/mol and
root mean square deviation of hGPR40-ZINC70692253 is around 3.5 Å in 20 ns of simulation.
Conclusion: Successful application of structure-based computational screening gave a novel candidate
from Natural Product library for diabetes treatment. So, Natural compounds may tend to cure diabetes
with lesser extent of undesirable effects in comparison to synthetic compounds and these novel screened
compounds may show a plausible biological response in the hit to lead finding of drug development
process. To the best of our knowledge, this is the first example of the successful application of SBVS to
discover novel natural hit compounds using hGPR40.