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.

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 cells of accuracy. this the and are evaluate IRLC, we first define M the mean conservation score of N residues within a predicted where C is the conservation score representing the of peptide conservation of a residue in position of the neo-ligand like be calculated by any suitable while our experiment, position evaluate we A motif molecule will be as a false prediction if some if much conserved than is contradicts domains which in turn leads to select, fragmenter, identified all of potential fragment-protein interactions. Benchmarking with known drug-protein interactions shows that our proposed methodology outperforms previous methods that exploit either protein sequences or compound structures to predict drug targets, which demonstrates the predictive power of our proposed BiogenetoligandorolTM KNIME-based referenced based GA(M)E-QSAR PDTCD method. We propose a ligand-based approach to the selection of conserved active pharmacophpric fragments with positive contribution to biological immunogenic activity, developed on the basis of the KNIME-BiogenetoligandorolTM-PASS-KNIME-based GA(M)E-QSAR algorithm. The robustness of our novel cluster of chemical iniformatic stochastic low mass algorithm for heterogeneous datasets has been shown earlier. PASS can estimate qualitative (yes/no) prediction of biological activity spectra for over 4000 biological activities and, therefore, provides the basis for the preparation of a fragment library corresponding to multiple criteria. Our novel cluster of algorithms for the prediction of the total free energy interactive binding between the conserved fragment-based pharmacophore top ranked selected has been validated using the fractions of intermolecular interactions calculated for known inhibitors of nine MAGED4B peptides extracted from the Protein Data Bank database. A novel docking algorithm called as FIPSDock, which implements a variant of the Fully Swarm (FIPS) optimization method and adopts the newly developed energy function of AutoDock 4.20 suite for solving flexible protein-ligand docking problems was also added as a standart fingerprinting inteaction tool to improve our search ability and docking accuracy which was first evaluated by multiple cognate docking experiments. More importantly, our multi-covalent hyper ligand structure 4D reverse Docking methodology was evaluated against PSO@AutoDock, SODOCK, and AutoDock 4.20 suite by cross-docking experiments of 174 protein-ligand complexes among eight protein targets (CDK2, ESR1, F2, MAPK14, MMP8, MMP13, PDE4B, and PDE5A) derived from Sutherland-crossdock-set. The PBE combines the continuum electrostatics description of fixed charges in a dielectric medium with the Boltzmann prescription for mobile ions in aqueous solvent at the thermal equilibrium in silico strategy:A flow-driven the ImgLib2 the the an efficient haplotype phasing algorithm based on scalable sliding windows within GRID-based three-dimensional pharmacophores in PharmBench workflow a benchmark data set for evaluating pharmacophore elucidation methods. a mimicking properties for the possible increasement of the Muscle Mass Fiber Size towards Wnt7a/Fzd7 to the Akt/mTOR Anabolic -I/MAPK/ERK pathways utilising (Propeptide-Fc)/MGF phage-displayed random peptide libraries through a KNIME-RDkit-CDK