GASS-WEB: a web server for identifying enzyme active sites based on genetic algorithms

João P. A. Moraes, Douglas E. V. Pires*, Gisele L. Pappa, Sandro C. Izidoro*

Abstract

Structure-guided methods have been proposed over the years to infer protein function based on active site similarity. Given an active site template, these methods use different mathematical modelling and searching procedures to match the template to a given set of proteins. Many of the current available methods present, however, limitations such as performing only exact matches on template residues (not accounting for conservative changes), pruning the search space using ad-hoc procedures, besides finding inter-domain active sites. In order to tackled these problems, we have recently proposed GASS (Genetic Active Site Search), a search method based on genetic algorithms that aims to cope with the aforementioned issues. Here we propose a user-friendly web server implementing the method’s capabilities, called GASS-WEB.

GASS-WEB can be used under two different scenarios: (a) given a protein of interest, to try to match a set of specific templates (i.e., known active sites); or (b) given an active site template, looking for it in a database of protein structures.

The method has shown to be very effective on a range of experiments. Based on the Catalytic Site Atlas (CSA) annotation, it was able to correctly identify >90% of the catalogued active sites. It also managed to achieve a MCC of 0.63 on the CASP 10 data set (ranking fourth among 18 methods).

Papers

IZIDORO, S. C.; DE MELO-MINARDI, R. C.; PAPPA, G. L. GASS: identifying enzyme active sites with genetic algorithms. Bioinformatics (Oxford. Print), v. 31, p. 864-870, 2015.

IZIDORO, SANDRO; LACERDA, ANISIO M.; PAPPA, GISELE L. MeGASS: Multi-Objective Genetic Active Site Search. Genetic and Evolutionary Computation Conference - GECCO 2015, Madrid, Spain.

MORAES, J.P.A.; PAPPA G. L.; PIRES D.E.V.; IZIDORO, S.C.; GASS-WEB: a web server for identifying enzyme active sites based on genetic algorithms. Nucleic Acids Res 2017 gkx337. doi: 10.1093/nar/gkx337

Available Resources

CSA templates	Performs active site search using literature-derived and PSI-BLAST templates from CSA, given a PDB file.
NCBI-VAST database	Performs active site search using a user-provided template on the NCBI-VAST database.
CSA binding sites	NEW: Performs binding site search using literature-derived and PSI-BLAST templates from CSA, given a PDB file.