Molecular Docking of Beta Tricalcium Phosphate Combined with Dicalcium Phosphate Dihydrate Compared to Hydroxyapatite induced Osteogenesis Biomarker: A Bioinformatic Approach

Combining beta-tricalcium phosphate (β-TCP) with other materials may be promising to expand its therapeutic applications, especially in bone regeneration. Dicalcium phosphate dihydrate (DCPD), which has the highest solubility among calcium phosphates at physiological conditions, may escalate β-TCP osteoinductivity. The aims of this study are to analyze β-TCP, DCPD, β-TCP combined with DCPD, and hydroxyapatite (HA) to induce osteogenesis through molecular docking. This study uses ligands consisting of β-TCP, HA, and DCPD from PubChem. Ligand binding targets consisting of bone morphogenic protein-2/-4/-7 (BMP-2), BMP4, BMP7, fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), insulin growth factor-1 (IGF1), platelet-derived growth factor (PDGF), runt-related transcription factor-2 (runx2), Osterix, alkaline phosphatase (ALP), osteocalcin, osteonectin, osteopontin, and Coll1a1 were obtained from RCSB PDB. PyMol v2.5 was used to remove ligands and contaminants, such as water, for the optimization of molecular docking simulation. The ligand with the best activity is predicted to affect the activity of the target protein to trigger specific biological responses of osteogenesis biomarkers and predicted through Cytoscape v3.10.1. The combination of BTCP and DCPD has a higher binding affinity to osteogenic biomarkers, such as BMP-2, BMP4, BMP7, FGF-2, VEGF, TGF-β, IGF1, PDGF, RUNX2, Osterix, ALP, osteocalcin, osteonectin, osteopontin, and Coll1a1 compared with HA, BTCP alone, and DCPD alone. The combination of BTCP and DCPD has proven its superior potential as a synthetic bone substitute material compared with HA, BTCP alone, and DCPD alone by inducing osteogenic biomarkers as documented in silico.