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Glycoprotein-96, a non-polymorphic heat-shock protein, associates with intracellular peptides. Autologous tumor-derived heat shock protein-peptide complex 96 (HSPPC-96) can elicit potent tumor-specific T cell responses and protective immunity in animal models. Chemokines were described originally in the context of providing migrational cues for leukocytes. They are now known to have broader activities, including those that favor tumor growth. Treatment with autologous tumor-derived HSPPC-96 was feasible and safe at all doses tested. Observed immunological effects and antitumor activity were modest, precluding selection of a biologically active dose. Coevolution between proteins is crucial for understanding protein-protein interaction. Simultaneous changes allow a protein complex to maintain its overall structural-functional integrity. In this Research Scientific Project, we combined statistical coupling analysis (SCA) and molecular dynamics simulations on thecomplex-96 (HSPPC-96) protein complex to evaluate coevolution between conserved binding protein domain regions. We reconstructed an inter-protein residue coevolution network, consisting of 37 residues and 37complex-96 (HSPPC-96) binding domains conserved peptide derived residues and its fitness scoring reverse ligand docking interactions. It shows that most of the coevolved residue pairs are spatially proximal. When the mutations happened, the stable local structures were broken up and thus the protein interaction was decreased or inhibited, with a following increased risk of melanoma. The identification of inter-protein coevolved residues in thecomplex-96 (HSPPC-96) complex can be helpful for designing protein drug target and in silico discovery of engineering novel nanomolecule experiments. In this scientific study we have in silico discovered a Unique Small Molecule Modulator of CXCR4 tumor-derived heat-shock protein peptide complex-96 (HSPPC-96) by identifying Hits of a High-Throughput Screen Identify the Hydrophobic Pocket of Autotaxin/Lysophospholipase D as an Inhibitory Surface Molecular dynamic simulation and statistical coupling analysis via a KNIME-based BiogenetoligandorolTM generated of a functional coevolution network of oncogenic mutations in the (HSPPC-96) hyper-interactive multicovalent annotated pharmacophore construct complexes.

Article Type

Research Article – Abstract

Publication history

Received: Sep 20, 2017
Accepted: Sep 25, 2017
Published: Oct 01, 2017


Grigoriadis Ioannis, Grigoriadis George, Grigoriadis Nikolaos, George Galazios (2017) In silico development of a unique fragment poly-pharmacologic modulator of CXCR4 tumor-derived heat-shock GGHFGPFDY peptide mimotopic complex-96 (HSPPC-96) by highthroughput identifying hits in the hydrophobic autotaxin/lysophospholipase D pocket.

Authors Info

Grigoriadis Nikolaos
Department of IT Computer Aided Personalized Myoncotherapy, Cartigenea-Cardiogenea, Neurogenea-Cellgenea, Cordigenea-HyperoligandorolTM,
Biogenea Pharmaceuticals Ltd,
Thessaloniki, Greece;

Grigoriadis Ioannis
Department of Computer Drug Discovery Science, BiogenetoligandorolTM,
Biogenea Pharmaceuticals Ltd,
Thessaloniki, Greece;

Grigoriadis George
Department of Stem Cell Bank and ViroGeneaTM,
Biogenea Pharmaceuticals Ltd,
Thessaloniki, Greece;

George Galazios
Professor of Obstetrics and Gynecology,
Democritus University of Thrace,
Komotini, Greece;


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