Rational Design and Optimisation of a Bioactive Cyclic mimetic-Peptide Pharmacophoric hyperagonist for the in silico Generation of a Down-Regulator of TNF Secretion by Investigating Drug-Target Association and Dissociation Mechanisms.

: Although strong binding interactions between protein receptor and ligand do not require the participation of a large number of amino acids in either site, short peptide chains are generally poor at recreating the types of protein-protein interactions which take place during cell recognition and signalling process, probably because their flexible backbones prevent the side chains from forming sufficiently rigid and stable epitopes, which can take part in binding with the desired strength and specificity. In a recently-reported Research and Scientific Project, it was shown that a proto-epitope containing F, R and S amino acids has the ability to down-regulate TNF secretion by macrophages. Here, in Biogenea Pharmaceuticals Ltd we discovered for the first time the GENEA-Bicytonafer-2889. A Rational Designed and Optimised Bioactive Cyclic mimetic-Peptide Pharmacophore for the Generation of a Down-Regulator of TNF Secretion by Investigating Drug-Target Association and Dissociation Mechanisms Using Metadynamics-Based Algorithms