Molecular Modeling of Human 3β-Hydroxysteroid Dehydrogenase Type 2: Combined Homology Modeling, Docking and QSAR Approach
Abstract: A homology model of
human 3β-HSD type 2 has been developed from homology modeling techniques using
Phyre2 server and refi ned by ModRefi ner. The PROCHECK, QMEAN and ProSA-webonline
tools were carried out to evaluate the stereochemical quality of the model. The
Ramachandranplot resulted from PROCHECK showed that 84.5% residues are in the
most favored region, 13.7% are inthe additional allowed region, 1.5% are in the
generously allowed region and 0.3% are in the disallowedregion. The QMEAN (Z-score)
are 0.509 (-3.006) and Z-score of ProSA-web is -7.10. The negativevalues of
protein fold energies also found in almost all sequences. Furthermore,
molecular docking wasalso applied to validate the model using MOE. The hydrogen
bonding interactions with Tyr154, Ser124,and Ser218 are found in all docked
substrates as well as known inhibitors (trilostane and epostane). A dataset of
azasteroid inhibitors were also docked into the substrate active site of human
3β-HSD2. These docked structures were utilized to construct corresponding
docking-based QSAR equation by employing genetic algorithm (GA) statistical
analysis. The contructed best QSAR equation has a robust predictive power
according to its statistical parameters, hence may be applied to supersede the
default scoring function provided by docking software. These results indicate
that the human 3β-HSD2 model was successfully evaluated as a good model.
Keywords: human 3β-HSD2,
homology modeling, docking, QSAR
Penulis: BAMBANG SULISTYO ARI
SUDARMANTO , AGUSTINUS YUSWANTO, RATNA ASMAH SUSIDARTI, SRI NOEGROHATI
Kode Jurnal: jpfarmasidd170178
