Molecular Docking of some Herbal-based Potential Anti-psoriasis Agents with Dihydrofolate Reductase

Objectives: To find out the herbal inhibitor for Dihydrofolate reductase (DHFR) in replacements of some existing drugs like methotrexate to reduce side effects in psoriasis and also to cure psoriasis. Methods: Computational simulation techniques are used for molecular docking of few herbals like beta-santalol, quercetin, carvacrol, curcumin and ferulic acid into DHFR by using AutoDock 4.0. Online tool and databases like Qsite-finder, PDB, and Chemspider are also used to retrieve active sites and 3D structures of enzymes and inhibitors. Parameters like binding energy, intermolecular energy, inhibition constant and H-bonding between ligands and target are used to determine extent of inhibition. Results: This information could be supportive for new drug design for psoriasis, in which these potential inhibitors should interact strongly with above mentioned residues. In our study on the basis of minimum binding energy and inhibition constant we concluded that β-santalol was found to be best. β-Santalol interacted with DHFR and gives minimum binding energy - 6.85 Kcal/mol and inhibition constant 9.48 µm, it is also formed two H-bond with the active site residue Tyr121 of the DHFR. As this study utilized herbals which are unique with respect to inhibit DHFR and it could be better prospect on for methotrexate which is responsible for side effects if alone is used. This is the important initiation to in utilization of herbals for such target inhibition. Conclusion: DHFR is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as electron donor. Tetrahydrofolate and its derivatives are essential for purine synthesis, which are important for cell proliferation and cell growth Therefore these herbals will block the reduction of dihydrofolic acid to tetrahydrofolic acid and inhibit the synthesis of nucleic acid precursor in not only psoriasis but in other such disease as well.