A theoretical insight in interactions of some chemical compounds as mTOR inhibitors

Bulletin of the National Research Centre

Riadh Sahnoun¹  Greatman C. Okafor¹  Jibrin Noah Akoji¹  Karimatu Lami Abdullahi¹  David Ebuka Arthur¹  Samira A. Abdullahi¹  Charles Mgbemena² 

[1] Department of Chemistry, Baze University, Abuja, Nigeria;Department of Microbiology, Federal University of Technology, Minna, Nigeria;

关键词: SBDD;    Molecular docking;    Binding energy;    Hydrophobic interaction;    Hydrogen interaction;    Drug;   

DOI  :  10.1186/s42269-021-00525-x

来源: Springer

【 摘 要 】

BackgroundA series of known Food and Drug Administration (FDA) approved anticancer drugs were collected from the literature and docked against mTOR receptor which has been identified in present time as a target for therapeutic anticancer agents. The compounds binding affinity were calculated after minimising the interaction within the binding pockets’ of the mTOR (4JT6) receptor.ResultsThe result shows that PF-04691502 ligand best inhibited mTOR while occupying the Adenosine triphosphate (ATP)-binding site on the receptor. PF-04691502 had the best binding affinity with a reported value of − 39.261 kcal/mol, and a hydrogen bond energy contribution of − 8.326 kcal/mol. Polamid529 is also found to have a good binding affinity of − 36.75 kcal/mol with the receptor, but was less significant than that calculated for the reference or standard inhibitor (X6K) used (− 37.862 kcal/mol). Further analysis revealed that Palomid529 formed a more stable complex with the receptor than torin2 and X6K due to the significant hydrogen bond contributions it adds to its overall binding score.ConclusionPF-04691502 ligand was identified as the best inhibitor due to its high binding affinity for mTOR and should be considered as the best alternative to the reference inhibitor X6K.

【 授权许可】

CC BY