Automated drug design of kinase inhibitors to treat Chronic Myeloid Leukemia

• Published in: Journal of molecular graphics & modelling Vol. 91; pp. 52 - 60
• Main Authors: Malkhasian, Aramice Y.S., Howlin, Brendan J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2019
• Subjects: Drug design; Imatinib; Leukemia; Molecular design; Molecular design; Imatinib; Drug design; Leukemia
• ISSN: 1093-3263; 1873-4243
• DOI: 10.1016/j.jmgm.2019.05.014

Medicinal chemistry has in the past been dominated by learned insights from experienced organic chemists. However, with the advent of computer based methods, computer aided drug design has become prominent. We have compared here the ability of locally sourced expert medicinal chemists to purely automated methods and found that the automated method produces a better potential candidate drug than the expert input. The example chosen is based on inhibitors to Abl-kinase and the successful anti-leukaemic drug imatinib. The proposed molecule is a simple modification of nilotinib and has a docking energy of 4.2 kJ/mol better than the best intuitive molecule. Automatic drug design improves binding energy by 6 kJ/mol. [Display omitted] •Automated drug design scores over intuitive drug design by producing a best binding energy ligand from a simple modification of nilotinib.•In a shorter time one can develop new drugs to overcome resistance of drugs or find better effective drugs.•In addition this computational procedure is much faster than conventional method which uses free energy calculations.•This work was presented at the 2nd international conference on pharmaceutical chemistry.