Molecular modeling investigation of the potential mechanism for phytochemical-induced skin collagen biosynthesis by inhibition of the protein phosphatase 1 holoenzyme.

The most prominent feature of UV-induced photoaged skin is decreased type 1 procollagen. Increase of the TGF-β/Smad signaling through inhibition of the TβRI dephosphorylation by the GADD34-PP1c phosphatase complex represents a promising strategy for the increase in type 1 collagen production and prevention of UV-induced skin photoaging. In this study, the molecular docking and dynamics simulations, and pharmacophore modeling method were run to investigate a possible binding site as well as binding modes between apigenin, daidzein, asiaticoside, obovatol, and astragaloside IV and PP1c. Through docking study, the possible binding site for these phytochemicals was predicted as the hydrophobic (PP1-substrate binding) groove. The result indicates that PP1 is the significant target of these compounds. Moreover, the 20,000-ps MD simulations present that the binding locations and modes predicted by the docking have been slightly changed considering that the MD simulations proffer more reliable details upon the protein-ligand recognition. The MM-GBSA binding free energy calculations and pharmacophore modeling rationally identify that the highly hydrophobic surfaces/pockets at close proximity of the catalytic core are the most favorable binding locations of the herbal compounds, and that some experimental facts upon a possible mechanism of increase in collagen biosynthesis can be explained. The present study theoretically offers the reliable binding target of the herbal compounds, and therefore helps to understanding the action mechanism for natural small molecules that enhance collagen production.