Protein engineering studies for C-C chemokine receptor type 2 (CCR2)

C-C chemokine receptor type 2 (CCR2) belongs to large GPCR family and it plays a critical role in cognitive function. Inhibition of CCR2 is important for autoimmune diseases including atherosclerosis, pain, and metabolic diseases. 3D structure of this receptor was not solved yet. In the current study, 3D structure of the CCR2 is predicted using recently solved high resolution crystal structure of C-C chemokine receptor type 5 (CCR5) which shares a high amino acid sequence homology with CCR2. Derived model firstly refined with molecular dynamics simulations and then validated with Ramachandran plot as well as available validation tools such as PROCHECK (a program to check the sterochemical quality of protein structures). Correctness of the topology of the binding cavity of the target structure is externally tested with known CCR2 inhibitors using molecular docking simulations. In addition, in order to discover novel CCR2 inhibitors through approved drugs, high throughput virtual screening of marketed drugs against derived CCR2 model was performed.