A neural network approach to evaluate fold recognition results

Fold recognition techniques assist the exploration of protein structures, and web-based servers are part of the standard set of tools used in the analysis of biochemical problems. Despite their success, current methods are only able to predict the correct fold in a relatively small number of cases. We propose an approach that improves the selection of correct folds from among the results of two methods implemented as web servers (SAMT99 and 3DPSSM). Our approach is based on the training of a system of neural networks with models generated by the servers and a set of associated characteristics such as the quality of the sequence-structure alignment, distribution of sequence features (sequence-conserved positions and apolar residues), and compactness of the resulting models. Our results show that it is possible to detect adequate folds to model 80% of the sequences with a high level of confidence. The improvements achieved by taking into account sequence characteristics open the door to future improvements by directly including such factors in the step of model generation. This approach has been implemented as an automatic system LIBELLULA, available as a public web server at http://www.pdg.cnb.uam.es/servers/libellula.html. © 2003 Wiley-Liss, Inc.