Identification of Dual Natural Inhibitors for Chronic Myeloid Leukemia by Virtual Screening, Molecular Dynamics Simulation and ADMET Analysis

AbstractChronic myeloid leukemia (CML) is a disease of bone marrow stem cells caused by excessive growth and accumulation of granulocytes in the blood. Aberrant expression of the BCR-ABL proteins in bone marrow stem cells have found out in 95  % cases of CML. Tyrosine Kinase domains (SH2 and SH3) of BCR-ABL proteins are the potent targets to inhibit the process. Initially, imatinib is preferred as an efficient inhibitor to control functional activity of disease. Recently, it has been reported that the advanced stage of CML developed res istance against imatinib. In continuation, dasatinib is the first drug to combat against this disease by targeting multiple receptors and proven better as compared to imatinib. Here, an attempt has been made to identify similar analogs of dasatinib. Virtual screening was performed against various na tural compound databases to get some potent natural compounds which are able to inhibit more than one receptor. Binding affinity of screened natural compounds was compared with some of the well-known inhibitors like imatinib, dasatinib, nilotinib etc., by analyzing their docking score and binding ef ficiency with the receptor. Stability of the best ligand–receptor complex was checked by performing 10 ns molecular dynamics simulation. ADMET properties of the obtained screened compounds were analyzed to check drug like property. Based on the aforementioned analysis, it has been suggested that t hese screened potent compounds are capable to inhibit...
Source: Interdisciplinary Sciences, Computational Life Sciences - Category: Bioinformatics Source Type: research