Investigation of molecular modeling method of rho-kinase (ROCK) inhibitors

Rho-kinase (ROCK) is a member of the serine / threonine protein kinase family and is approximately 160 kDa in weight. This enzyme has two isoforms, ROCKI and ROCKII, which are excreted in all cells in both enzymes. It is known that ROCKI is excreted more in the lung, liver, spleen, kidney and testicular, and ROCKII in the brain and muscle cells. ROCK, which interacts with Rho, is active in many different cellular functions, including smooth muscle contraction, cell growth, adhesion, migration, motility, gene expression, and apoptosis. These effects regulate the invasion and metastatic activities of cancer cells. ROCK inhibitors have been shown to reduce these cellular functions and suppress metastasis in cancer cells. This study aimed to determine the mechanism of interaction at the atomic level by the molecular docking study of 156 inhibitor constructs showing therapeutic potential as a result of experimental studies against ROCKI and ROCKII enzymes. As a result of this analysis, both enzyme-specific interaction regions were determined and it was observed that amino acids Arg100, Ala119, Lys121, Ala213 and Asp218 were more commonly interacted with Val90, Lys105, Val137, Asp160, Asp202 and ROCKII for ROCKI. With this information, it will be possible to treat diseases for which ROCK is involved by developing more effective and specific ROCK inhibitors for the determined interaction region of the enzymes.