Computational Study of Triterpenoids of Ganoderma lucidum with Aspartic Protease Enzymes for Discovering HIV-1 and Plasmepsin Inhibitors

Abstract

See, stats, and : https : / / www. researchgate. net/ publication/ 271967334 Computational Ganoderma Enzymes 1 Inhibitors Article DOI : 10 . 5539 / ijc . v7n1p62 CITATION 1 READS 41 3 , including : Jutti Universitas 32 SEE All text , letting . Available : Jutti Retrieved : 05 Abstract Rapid resistance development of HIV 1 and Plasmodium falciparum parasite requires discovery of more potent new drugs . Aspartic protease enzymes expressed by HIV 1 and P . falciparum could be used as important drug targets . The catalytic site is located at the bottom of a cleft in the enzyme surface and consists of triad Asp25 , Thr26 , Gly27 . Important aspartic acids are Asp32 and Asp215 . Aspartic proteases are inhibited by pepstatin A , a naturally occurring peptide containing two statins , which replace the amino acids . The hydroxyl group of the statin binds tightly to the catalytically active aspartic acid residues in the active site of protease , thereby mimicking the transition state of the peptide cleavage . Previous study proved that ganoderiol F , a triterpenoid isolated from the stem of Ganoderma sinense showed higher affinity towards HIV 1 protease (binding energy= 11 . 40 kcal / mol and K i = 4 . 68 nM) than to plasmepsin I (binding energy= 9 . 96 kcal / mol and K i = 50 . 94 nM) . In this paper , computational studies of G . lucidum triterpenoids with aspartic protease enzymes of HIV 1 and plasmepsin I , were performed using AutoDock 4 . 2 . Nelfinavir and KNI 10006 were used as the standards for HIV 1 protease and plasmepsin I , respectively . The four triterpenoids are able to interact with both enzymes . Ganoderat acid B showed the best affinity to HIV 1 protease (binding energy= 7 . 49 kcal / mol and Ki= 0 . 001 mM) which is better than nelfinavir . Furthermore , the best affinity to Plasmepsin I is showed by ganodermanondiol (binding energy= 7 . 14 kcal / mol and Ki= 0 . 005 mM which is better than KNI 10006 . According to the values of binding energy and inhibition constant , triterpenoids of G . lucidum could be developed further as both anti HIV and anti malaria .