Molecular docking studies of lichen metabolites as malarial protein inhibitors: Plasmepsin II protease and dihydro fola te reductase
E. Susithra, Sumer Singh Meena, D. Chamundeeswari, Rajasekhar Chekkara, Ethiraj Varalakshmi · 2014
Plasmepsin II (PL II), an aspartyl protease inhibit or of P. falciparum, plays a key role in the haemog lobin degradation inside the food vacuole. Besides, dihyd rofolate reductase (DHFR), a small enzyme that play s a critical role in the building of DNA and other processes, is found to be involved in the reproduction of the pa rasites, P. falciparum and P. vivax. Recently more focus has be en arrived in the treatment and cure of malaria thr ough inhibition of these key enzymes, PL II protease and DHFR. The main aim of the present study is to find out the binding mode and hydrogen bond interactions of the lichen metabolites; depsides viz. atranorin (ATR) & lecanoric acid (LA), depsidone, salazinic acid (SA) and diben zofuran, usnic acid (USA) derivatives with PL II pr otease and DHFR proteins through molecular docking simulations using glide module v5.5 (Schrodinger suite 2009) b y flexible docking method. The docking results indicate that t he dibenzofuran USA derivatives are showing impress ive hydrogen bond and hydrophobic interactions with PL II protease, whereas the depsidone, SA shows satisf actory interactions and the depsides namely, ATR and LA wi th least interactions. With respect to the DHFR, de psides; ATR and LA are showing effective H-bond interactions wi th the DHFR protein active sites of the two species in different docking grids. Further, SA and USA derivatives are showing flat interactions with the active residues of the DHFR protein. From the above results, it is clearly evid ent that further studies can be attempted in design ing similar such structure-based novel molecules with PL II and DHFR inhibitory activity.