Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.24 (
mitogen-activated protein kinase
)
95,810
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Candida albicans
, fungal yeast causes several lethal infections in immune-suppressed patients and recently emerged as drug-resistant pathogens worldwide. The present study aimed to screen putative drug targets of
Candia albicans
and to study the binding potential of novel natural lead compounds towards these targets by computational virtual screening and molecular dynamic (MD) simulation. Through extensive analysis of
mitogen-activated protein kinase
(
MAPK
) signalling pathways,
mitogen-activated protein kinase
-1 (HOG1) and cell division control protein-42 (CDC42) genes were prioritized as putative targets based on their virulent functions. The three-dimensional structures of these genes, not available in their native forms, were computationally modeled and validated. 76 lead molecules from various natural sources were screened and their drug likeliness and pharmacokinetic features were predicted. Among these ligands, two lead molecules that demonstrated ideal drug-likeliness and pharmacokinetic features were docked against HOG1 and CDC42 and their binding potential was compared with the binding of conventional drug
Fluconazole
with their usual target. The prediction was computationally validated by MD simulation. The current study revealed that Cudraxanthone-S present in
Cudrania cochinchinensis
and Scutifoliamide-B present in
Piper scutifolium
exhibited ideal drug likeliness, pharmacokinetics and binding potential to the prioritized targets in comparison with the binding of
Fluconazole
and their usual target. MD simulation showed that CDC42-Cudraxanthone-S and HOG1-Scutifoliamide-B complexes were exhibited stability throughout MD simulation. Thus, the study provides significant insight into employing HOG1 and CDC42 of
MAPK
as putative drug targets of
C. albicans
and Cudraxanthone-S and Scutifoliamide-B as potential inhibitors for drug discovery.Communicated by Ramaswamy H. Sarma.
...
PMID:Mitogen activated protein kinase-1 and cell division control protein-42 are putative targets for the binding of novel natural lead molecules: a therapeutic intervention against
Candida albicans
. 3162 62
