INHIBITORS FOR SECA1 OF MYCOBACTERIUM TUBERCULOSIS H37RV
Zahra M. Al-Khafaji*, Marium B. Mahmood and Aaisha B. Mahmood
Background: Mycobacterium tuberculosis causes tuberculosis (TB), an infectious disease, needs an urgent intervention due to emergence of highly drug resistant strains. Aim: The study aimed to find out new inhibitors for strategic target (Translocase protein, SecA1, with pdb ID 1nkt), through building QSAR models using different descriptors of the available inhibitors of SecA protein. Materials and Methods: About 50 molecules that inhibit SecA in different microorganisms were collected from different sources, descriptors of these molecules were calculated and used to build QSAR regression models using Multiple Linear Regression (MLR). Results: Built model was satisfied most statistical requirements, used to estimate the IC50 of different molecules included in Zinc database, the virtual screening revealed about 104 molecules or ligands under strict restrictions. Docking studies showed that most obtained molecules docked strongly in the target protein (1nkt). The binding affinities ( -5.9 to -9.2 kcal/mol), using RMSD value of zero. Further filtration and testing resulted in five molecules which can be used and applied as inhibitor to this protein.
Keywords: Mycobacterium tuberculosis, SecA1 inhibitors, QSAR, Drug discovery.
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