Now showing 1 - 2 of 2
  • Publication
    Ab initio and template-based prediction of multi-class distance maps by two-dimensional recursive neural networks
    Background: Prediction of protein structures from their sequences is still one of the open grand challenges of computational biology. Some approaches to protein structure prediction, especially ab initio ones, rely to some extent on the prediction of residue contact maps. Residue contact map predictions have been assessed at the CASP competition for several years now. Although it has been shown that exact contact maps generally yield correct three-dimensional structures, this is true only at a relatively low resolution (3ā€“4 ƅ from the native structure). Another known weakness of contact maps is that they are generally predicted ab initio, that is not exploiting information about potential homologues of known structure. Results: We introduce a new class of distance restraints for protein structures: multi-class distance maps. We show that C trace reconstructions based on 4-class native maps are significantly better than those from residue contact maps. We then build two predictors of 4-class maps based on recursive neural networks: one ab initio, or relying on the sequence and on evolutionary information; one template-based, or in which homology information to known structures is provided as a further input. We show that virtually any level of sequence similarity to structural templates (down to less than 10%) yields more accurate 4-class maps than the ab initio predictor. We show that template-based predictions by recursive neural networks are consistently better than the best template and than a number of combinations of the best available templates. We also extract binary residue contact maps at an 8 ƅ threshold (as per CASP assessment) from the 4-class predictors and show that the template-based version is also more accurate than the best template and consistently better than the ab initio one, down to very low levels of sequence identity to structural templates. Furthermore, we test both ab-initio and template-based 8 ƅ predictions on the CASP7 targets using a pre-CASP7 PDB, and find that both predictors are state-of-the-art, with the template-based one far outperforming the best CASP7 systems if templates with sequence identity to the query of 10% or better are available. Although this is not the main focus of this paper we also report on reconstructions of C traces based on both ab initio and template-based 4-class map predictions, showing that the latter are generally more accurate even when homology is dubious. Conclusion: Accurate predictions of multi-class maps may provide valuable constraints for improved ab initio and template-based prediction of protein structures, naturally incorporate multiple templates, and yield state-of-the- art binary maps. Predictions of protein structures and 8 ƅ contact maps based on the multi-class distance map predictors described in this paper are freely available to academic users at the url http://distill.ucd.ie/.
    ScopusĀ© Citations 42  442
  • Publication
    Distill : a suite of web servers for the prediction of one-, two- and three-dimensional structural features of proteins
    We describe Distill, a suite of servers for the prediction of protein structural features: secondary structure; relative solvent accessibility; contact density; backbone structural motifs; residue contact maps at 6, 8 and 12 Angstrom; coarse protein topology. The servers are based on large-scale ensembles of recursive neural networks and trained on large, up-to-date, non- redundant subsets of the Protein Data Bank. Together with structural feature predictions, Distill includes a server for prediction of CĪ± traces for short proteins (up to 200 amino acids). The servers are state-of-the-art, with secondary structure predicted correctly for nearly 80% of residues (currently the top performance on EVA), 2-class solvent accessibility nearly 80% correct, and contact maps exceeding 50% precision on the top non-diagonal contacts. A preliminary implementation of the predictor of protein CĪ± traces featured among the top 20 Novel Fold predictors at the last CASP6 experiment as group Distill (ID 0348). The majority of the servers, including the CĪ± trace predictor, now take into account homology information from the PDB, when available, resulting in greatly improved reliability. All predictions are freely available through a simple joint web interface and the results are returned by email. In a single submission the user can send protein sequences for a total of up to 32k residues to all or a selection of the servers. Distill is accessible at the address: http://distill.ucd.ie/distill/.
    ScopusĀ© Citations 84  576