RSUSSH 2020
IN20-011 Blind Docking Study of Compound D and Dimethoxyphenylbutadiene (DMPBD) Against Cyclooxygenase-2
Presenter: Prasan Tangyuenyongwatana
Rangsit University, Thailand
Abstract
In this study, blind docking method was applied to discriminate against the ligand-protein binding of 4-(3,4-dimethoxyphenyl)but-1,3-diene (DMPBD) and (E)-(3,4-dimethoxyphenyl)but-3-en-1-ol (compound D) at the active site of cyclooxygenase-2 (COX-2). These two compounds can bind flawlessly in the COX-2 active site with nearly the similar docking energies with regular docking method but only DMPBD was the active compound (IC50 = 20.68 μM). Blind docking was achieved for the finding of the possible binding site of ligand by skimming the entire surface of COX-2 protein. Cyclooxygenase-2 (PDB ID: 1CX2, 1PXX, 3NTG) crystal structures were used in this research and the blind docking was run by PyRx 0.8 program. The experimental results of DMPBD at exhaustiveness 4 showed the positive binding ratio of DMPBD/compound D at the active site of three enzymes (1CX2, 1PXX, 3NTG) in the ratio values of 1.63, 2.08, and 2.43, respectively. That means DMPBD was more appropriate than compound D in binding with enzymes. These results demonstrated that there was some specificity of DMPBD to bind with the enzymes which may due to the low rotational bond and rigidity of DMPBD structure making it can easily reach to lower energy of the active site. While compound D which has more flexible and more polar structure was unable to give good conformation for lowest energy at exhaustiveness 4. These blind docking outcomes were compatible with the in-vitro test result. However, blind docking can work well with some enzymes. This technique has to be studied more about the parameters that concern with the searching.
Citation format:
Tangyuenyongwatana, P., & Sombutaree, M.. (2020). Blind Docking Study of Compound D and Dimethoxyphenylbutadiene (DMPBD) Against Cyclooxygenase-2. Proceeding in RSU International Research Conference, May 1, 2020. Pathum Thani, Thailand.QUESTIONS & ANSWERS
In addtion to the previously reported in vitro test, this work is a good alternative way to understand and explain the anti-COX-2 effect of the two active compounds.
1. As the author mentioned in the abstract, what other parameters should we concern in order to precisely understand the docking behavior of these two compounds?
2. In general, are there any limitations of this method compared to an in vitro study.
For the first question, the blind docking or focused docking were performed in silico which the receptor or enzyme in the docking method is regid which can not move as in the in vivo environment. So, the docking result will give the trend of binding between enzyme and ligand follow the docking score or scoring functions of the program. Water and ions in the cell are also other parameters that may cause the binding between enzyme and ligand give different result. However, the blind docking can give some information about ligand structure ability to set itself into the lowest energy to macth with the active site.
For the second question, Blind docking has limitation on the size of ligand that can be used. If ligand has too big in size, it can not adapt or insert into the active site which normally stays inside the enzyme. For small molecule, MW range 150-300 amu., this size of molecule should be fine for blind docking. Anyway, the Blind docking study has to confirm with the in vitro study.