Molecular docking based on construction of 4-a-sterol demethylase (CYP51) as an active site of Madurella mycetomatis by homology modelling
Abstract
Objectives: Eumycetoma is a tropical neglected infectious disease causing large tumorous lesions on mainly the extremities. The current treatment consists of a combination of antifungal therapy with azoles and surgery. In order to predict which azoles, have the highest binding capacity to their drug target, a homology model based on the CYP51 target was constructed and its validity was tested by docking some of the currently available triazoles along with a set of synthetic compounds. Methods: Madurella mycetomatis 14-u03b1-sterol demethylase (MmCYP51) Protein sequence (GenBank: KXX80456.1), was built using comparative modelling method using the SWISS MODEL server facilities. The best model which chosen was Aspergillus fumigatus 14-u03b1 sterol demethylase (AfCYP51) with PDB ID; 4UYM, with sequence identity 66.09% and resolution of 2.55u00c5. Coordinates which are conserved between the target and the template are copied from the template to the model. Insertions and deletions are remodelled using a fragment library. Side chains are then rebuilt. The 3D superposition of the target protein and the template was carried out, and the RMSD for alignment was determined. The docking study was conducted with the docking module of molecular operating environment (MOE) software. The compounds 3D structures were built with Chem3D software then were transferred and saved into MOE database, the energy of each compound was minimized by MMFF94x force field. Protein 3D structures were…
Read the paper
Related studies
- Challenges and opportunities with drug repurposing: finding strategies to find alternative uses of therapeutics
- Challenges in Chagas Disease Drug Development
- T Cell Specificity: A Great Challenge in Chagas Disease
- Benznidazole treatment leads to DNA damage in Trypanosoma cruzi and the persistence of rare widely dispersed non-replicative amastigotes in mice
- Rapid Molecular Detection of Terbinafine-resistant Dermatophytes
- Identifying novel drugs with new modes of action for neglected tropical fungal skin diseases (fungal skinNTDs) using an Open Source Drug discovery approach
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.