Simulation Study of Interactions Between Two Bioactive Components from and 5-Lipoxygenase.

Introduction: Compound D and DMPBD are compounds extracted from Plai or Roxb., which have antiasthmatic properties. Thai herbal pharmacopoeia have indicated that approximate 50% of Thai prescriptions for asthma contain Plai. However, the inhibition mechanisms of these compounds are not clearly known.

Methods: In this study, molecular docking and molecular dynamics (MD) simulations have been used to simulate complex systems and analyze molecular interactions between these compounds and protein target, 5-lipoxygenase (5-LO) enzyme, which is an enzyme involved with asthma symptoms.

Results: From our MD simulations, Compound D and DMPBD molecules bind at the same binding site of its natural substrate (arachidonic acid) on 5-LO enzyme, which is similar to the binding of commercial asthma drug (Zileuton). Molecular mechanics generalized born surface area binding energy calculations of the 5-LO complex with Compound D and DMPBD are -26.83 and -29.15 kcal/mol, respectively.

Conclusions: This work indicated that Compound D and DMPBD are competitive inhibitors, which are able to bind at the same 5-LO substrate binding site. This reveals opportunities for using Compound D and DMPBD as novel antiasthmatic drugs.