Please use this identifier to cite or link to this item:
Title: Glycine induced formation and druggability score prediction of protein surface pockets
Authors: Bongini, Pietro
Niccolai, Neri 
Bianchini, Monica
Keywords: Protein glycinization; neural networks; transient pockets; druggability score; protein-ligand interaction
Issue Date: 2019
Project: None 
Nowadays, it is well established that most of the human diseases which are not related to pathogen infections have their origin from DNA disorders. Thus, DNA mutations, waiting for the availability of CRISPR-like remedies, will propagate into proteomics, offering the possibility to select natural or synthetic molecules to fight against the effects of malfunctioning proteins. Drug discovery, indeed, is a flourishing field of biotechnological research to improve human health, even though the development of a new drug is increasingly more expensive in spite of the massive use of informatics in Medicinal Chemistry. CRISPR technology adds new alternatives to cure diseases by removing DNA defects responsible of genome-related pathologies. In principle, the same technology, however, could also be exploited to induce protein mutations whose effects are controlled by the presence of suitable ligands. In this paper, a new idea is proposed for the realization of mutated proteins, on the surface of which more spacious transient pockets are formed and, therefore, are more suitable for hosting drugs. In particular, new allosteric sites are obtained by replacing amino-acids with bulky side chains with glycine, Gly, the smallest natural amino-acid. We also present a machine learning approach to evaluate the druggability score of new (or enlarged) pockets. Preliminary experimental results are very promising, showing that 10% of the sites created by the Gly-pipe software are druggable.
ISSN: 0219-7200
DOI: 10.1142/S0219720019500264
Appears in Collections:Publications

Show full item record

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.