In silico determination of the affinity of some lactones against mitochondrial ClpP

ClpP is a serine protease found in the mitochondrial matrix, and it is unique in that it is found only in mitochondria. By digesting misfolded or damaged proteins, this protease contributes to mitochondrial protein quality control and the maintenance of normal metabolic activity. ClpXP is a multimeric complex composed of ClpX, an ATP-dependent unfoldase, and ClpP, a ring of heptamers that is both stable and active as a peptidase. ClpXP is overexpressed in both blood cancers and solid tumours, and it seems to be essential for the survival of a subset of cancers. In moreover, blocking or overactivating cancer cells treated with ClpXP exhibit diminished respiratory chain activity and eventually die. As a result, mitochondrial ClpXP targeting may represent a promising new approach to cancer therapy. In the presented study, we tried to determine the affinity of some lactone compounds for ClpP protein by molecular modeling method. The crystal structure of the protein was downloaded from the protein database with the code 6BBA. 3D structures of the molecules were obtained from the PubMed web page. According to the results obtained using the Molegro Virtual Docker program, Trichurusin K and Trichurusin J have the highest affinity for protein with -162.107 and -147.058 MolDock Scores. Detailed interaction maps of the molecules with the active site of the enzyme were displayed using the Discovery Studio 2021 Client program.