Molecular modelling and docking of Mus musculus HMGB1 inflammatory protein with CGA

Recently, High Mobility Group Box1 (HMGB1) protein has been reported as an inflammatory cytokine present in all nucleated cells with crucial role in the genesis and promotion of cancer. No HMGB1 protein mice model and its active site details are available to validate mice in vivo experiments. Here, for the first time we have reported in silico mice HMGB1 model using human HMGB1 template. Prepared HMGB1 secondary structure showed 6-α helices, 5-β turns, 2-γ turns with 67% α-helices, 32% coil and 9% turn without β-sheet, and classified as α-class protein. Ramachandran plot analysis showed 98.2% and 92.3% residues lies in favoured region, verified by RAMPAGE and PDBsum server respectively. Cancer atlas of HMGB1 protein showed up-regulated expression of HMGB1 gene in different cancer, proved by CAB (CAB005873) and HPA-antibody (HPA003506) in silico. HMGB1 protein showed interaction with different biologically important inflammatory protein as depicted in STRING result.Prominent active site has residues Tyr⁷⁸Ile⁷⁹Pro^80-81Lys⁸²Gly⁸³vGlu⁸⁴Thr⁸⁵Lys^86-88Phe⁸⁹Lys⁹⁰Asp⁹¹Pro⁹²Asn⁹³Tyr¹⁶²Lys¹⁶⁵ with 310 ų site volume.Interacting residues of CGA-HMGB1 docked complex were ILE⁷⁹PRO^80-81LYS⁸²GLY⁸³GLU⁸⁴LYS^86-88PHE⁸⁹Arg¹⁶³Ala¹⁶⁴LYS¹⁶⁵Gly¹⁶⁶ with docking score 3872 and surface area 412.6. CGA-conformer C3950 showed best docking than CGA and conformer-ZINC03947476, iso-chlorogenic acid and cischlorogenic acid. HMGB1 mice model could be a good therapeutic target for anti-cancerous drugs.