A predicted chemo-polypharmacophoric agent comprising (Propeptide-Fc)/MGF peptide mimicking interactive of high free binding energy properties towards Wnt7a/Fzd7 signalling Akt/mTOR anabolic growth IGF-I/PI3K/Akt -I/MAPK/ERK pathways. Grigoriadis Ioannis1, Grigoriadis George2 and Grigoriadis Nikolaos3* 1.Department of Computer Drug Discovery Science, BiogenetoligandorolTM, Thessaloniki, Greece, 2.Department of Stem Cell Bank and ViroGeneaTM, Biogenea Pharmaceuticals Ltd, Thessaloniki, Greece, 3.Department of IT Computer Aided Personalized Myoncotherapy, Cartigenea-Cardiogenea, Neurogenea-Cellgenea, Cordigenea-HyperoligandorolTM, ABSTRACT: The insulin-like growth factor-I (IGF-I) is a key regulator of skeletal muscle growth in vertebrates, promoting mitogenic and anabolic effects through the activation of the MAPK/ERK and the PI3K/Akt signaling pathways. Also, these results show that there is a time-dependent regulation of IGF-I plasma levels and its signaling pathways in muscle. The insulin-like growth factor-I (IGF-I) is a key regulatory hormone that controls growth in vertebrates. Particularly, skeletal muscle growth is strongly stimulated by this hormone. IGFI stimulates both proliferation and differentiation of myoblasts, as well as promoting myotube hypertrophy in vitro and in vivo. The mitogenic and anabolic effects of IGF-I on muscle cells are mediated through specific binding with the IGF-I receptor (IGF-IR). This ligand-receptor interaction promotes the activation of two major intracellular signaling pathways, the mitogen-activated protein kinases (MAPKs), specifically the extracellular signal-regulated kinase (ERK), and the phosphatidylinositol 3 kinase (PI3K)/Akt. The MAPK (RAF/MEK/ERK) is a key signaling pathway in skeletal muscle, where its activation is absolutely indispensable for muscle cell proliferation. Biologically active polypeptides derived from the E domain that forms the C-terminus of the insulin-like growth factor I (IGF-I) splice variant known as mechano growth factor which have been demonstrated neuroprotective and cardioprotective properties, as well as the ability to increase the strength of normal and dystrophic skeletal muscle. Ligands selected from phage-displayed random peptide libraries tend to be directed to biologically relevant sites on the surface of the target protein. Protein-peptide interactions form the basis of many cellular processes. Consequently, peptides derived from library screenings often modulate the target protein's activity in vitro and in vivo and can be used as lead compounds in drug design and as alternatives to antibodies for target validation in both genomics and drug discovery. In this research and science project we for the first time a predicted chemo-polypharmacophoric agent comprising (Propeptide-Fc)/MGF peptide mimicking properties for the possible increasement of the Muscle Mass Fiber Size towards Wnt7a/Fzd7 Signalling to the Akt/mTOR Anabolic Growth IGF-I/PI3K/Akt - I/MAPK/ERK pathways utilising (Propeptide-Fc)/MGF phage-displayed random peptide libraries through a KNIME-RDkit-CDK clustering pipeline. II METHODS Α Sequential Solution of the Poisson-Boltzmann Equation through a Combination Index Dynamic Unified Theorem for Multiple Entities: and when m ≠ 1, then: Based on Eqs. 1 and 2, in conjunction with Eq. 4, Chou and Talalay in 1983 introduced the term combination index (CI) for quantification of synergism (CI<1), additive effect (CI=1), and antagonism (CI>1) [6,13,14], where at x% inhibition, the general equation for two drugs is given below: A typical presentation of algorithms and graphics of CI values as a function of effect (fa) is illustrated in Figure 2. The resulting Fa-CI plot is also called Chou-Talalay plot. The Fa-CI plot and isobologram are two sides of the same coin, where Fa-CI plot is effect-oriented and the isobologram is dose-oriented (Figure 1). More details have been given in Reference 6. The algorithm for quantifying synergism or antagoni