Propedia: uma base de dados de estruturas de complexos proteína-peptídeo não redundante baseada em agrupamentos híbridos

Abstract

Protein-peptide interactions play in a wide variety of biological processes, such as cell signaling, regulatory networks, immune system, and enzyme inhibition. It is estimated that 40% of protein interactions are mediated by peptides, nevertheless, there is little structural data information available about these interactions. Peptides are polypeptide chains made up of few amino acids and therefore are more flexible and versatile. The peptides have a structural conformation of a transitory character, and therefore can be more easily manipulated. In addition, peptides in general have low toxicity and their normally small interface area make them attractive targets for therapeutic proposals, rational drug design and protein inhibitors. In fact, it is estimated that 10% of the pharmaceutical market be composed of peptide-based, which continues to rise. The present work presents a comprehensive and up-to-date database of protein-peptide complex structures, named Propedia. Propedia comprises over 19,000 high-resolution complex retrieved from the Protein Data Bank (PDB), adding new features about these protein-peptide interac- tions. Although there are other databases of protein-peptide structures, Propedia stands out for proposing hybrid clustering algorithm, in order to gather similar complexes and, consequently, remove redundancy, according to the researcher’s need. Propedia has three types of clustering: by peptide sequences; by protein-peptide interface structures; and by binding sites. Finally, case studies were carried out to validate the usefulness of Propedia in finding promising peptides for protein targets. Among them are a prediction of peptide structures to inhibit the main protease of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and also the main protease of the soybean caterpillar (Anticarsia gemmatalis hübner), considered an important defoliating pest that harms the production of soybean in Brazil. Propedia is available through a web service (http://bioinfo.dcc.ufmg.br/propediadb/), with a user- friendly and intuitive interface, in which users can explore and analyze complexes, download part or all of database. Propedia also allows submitting sequences or structure of interest to recover similar complexes considering the target peptide/protein primary structure or its binding site.