this kind of as cavity sizes, form complementarity, electro static likely and hydrophobicity.The part of alpha helical peptides in mediating quite a few PPIs is well demonstrated and development of smaller or ganic molecules mimicking this kind of peptides becomes im portant.Latest studies are already carried out on the complete Protein Information Bank so as to set up a druggability profile of alpha helix mediated PPIs and also to predict which of them could bind a modest molecule.More especially, terphenyl and its derivates are compact organic molecules mimicking one particular face of an alpha helical peptide, i. e. the side chains of 3 critical residues occupying positions i, i three and i seven or i, i 4 and i seven on the bound helix. It has been sug gested that terphenyl compounds can serve as pharma cological probes because these are membrane permeable.Terphenyl one and 2, which mimic the calmodulin binding face of smooth muscle myosin light chain kinase.
have been shown to inhibit the interactions of calmodulin together with the enzyme three five cyclic nu cleotide phosphodiesterase and with all the helical peptide C20W with the plasma membrane calcium pumps.Following the similarity among the calmodulin and human centrin two alpha helix binding web-sites, we recently recommended that terphenyl two could possibly also inhibit the interaction involving Cilengitide Integrin inhibitor HsCen2 and also a 17 residues pep tide of Xeroderma Pigmentosum Group C protein.Terphenyl derivates mimicking the alpha helical construction of p53 N terminal peptide inhibit the p53 MDM2 and the p53 HDM2 interactions.These molecules also mimic the alpha helical area of Bak BH3 domain, which binds BCL X2, therefore disrupting the BCL X2. Bak interaction.In this get the job done we carried out a computational examination so as to assess quite a few key physicochemical and surface properties of proteins acknowledged to interact with alpha helical peptides or to bind terphenyl and its derivatives.
We calculated the binding pocket volumes plus the fractal dimensions on the surface cavities to the entire protein and for the binding pockets. We identified quite a few simila rities and specificities characterizing such protein binding web pages that will be valuable for future growth of additional effective compact molecule inhibitors focusing on alpha helix binding proteins. Strategies In this R547 study we compared the sequence and surface prop erties from the investigated proteins. As a way to analyze the sequence similarities we carried out sequence alignment applying the CLUSTALW software program.Interacting residues in the protein protein interface when it comes to get hold of dis tances had been found making use of the ContPro online freely avai lable tool.We recognized the protein residues interacting with all the three key residues of the alpha helical peptide those relative positions are mimicked by terphenyl and its derivatives. The distance threshold was set to five for the side chain atoms.