In silico Rivaroxaban binding affinity to β-ketoacyl[ACP]synthase I: search for new pharmacophore

Abstract

The activity of Rivaroxaban as a representative of oxazolidinone series in relation to β-ketoacyl[ACP]synthase I has been studied in silico. Using the molecular docking methods, the binding sites of Rivaroxaban with protein have been identified. For the site providing the highest affinity of Rivaroxaban with protein (-10.26 kcal/mol), 4 clusters characterized by a number of runs greater than 15 have been analyzed. It was found that the specific position of the ligand within these clusters can be changed via mechanism providing a physiological response. Slight changes in the characteristics of the environment can lead to a transition from an energetically dominant position (BE = –10.26 kcal/mol) with predominantly hydrophobic interactions to another position (BE = –8.88 kcal/mol) with predominantly hydrophilic interactions. Dynamic transition discussed may cause a physiological response. The results of the study with a high degree of probability confirm the implementation of a specific mechanism of antimycobacterial action of Rivaroxaban through inhibition of the mycolate biosynthesis.