Abstract

ASARM-peptides are substrates and ligands for PHEX, the gene responsible for X-linked hypophosphatemic rickets (HYP). PHEX binds to the DMP1-ASARM-motif to form a trimeric-complex with α5β3-integrin on the osteocyte surface and this suppresses FGF23 expression. ASARM-peptide disruption of this complex increases FGF23 expression. A 4.2kDa peptide (SPR4) has been previously used that binds to ASARM-peptide and ASARM-motif to DMP1-PHEX interact and by assessing SPR4 for treating inherited hypophosphatemic rickets. Here, we discovered for the first time the GENEA-Bonespemitron-5527, a Computer-aided designed of a SPR4-peptide-mimetic pharmacophoric super-agonist for the regulation of bone metabolism utilizing Computational modelling of biomolecular simulation methods in structural biology interfaces between physics, chemistry and biology on an atomistic scalable literature computer-based discovery of an annotated SPR4-peptide-similar multi-molecular pharmacophoric reverse docked super-agonist scaffold as a canditate bone metabolism regulator.

Keywords

SPR4 peptide mimetic; pharmacophoric; super agonist; regulation; bone-metabolism; scalable Literature Based; β-catenin; Computational modelling; biomolecular systems; simulation methods; structural biology; interfaces; physics chemistry and biology in atomistic biomolecular simulation scalable literature;