Abstract
BackgroundResidue-residue contacts are key features for accurate de novo protein structure prediction. For the optimal utilization of these predicted contacts in folding proteins accurately, it is important to study the challenges of reconstructing protein structures using true contacts. Because contact-guided protein modeling approach is valuable for predicting the folds of proteins that do not have structural templates, it is necessary for reconstruction studies to focus on hard-to-predict protein structures.ResultsUsing a data set consisting of 496 structural domains released in recent CASP experiments and a dataset of 150 representative protein structures, in this work, we discuss three techniques to improve the reconstruction accuracy using true contacts – adding secondary structures, increasing contact distance thresholds, and adding non-contacts. We find that reconstruction using secondary structures and contacts can deliver accuracy higher than using full contact maps. Similarly, we demonstrate that non-contacts can improve reconstruction accuracy not only when the used non-contacts are true but also when they are predicted. On the dataset consisting of 150 proteins, we find that by simply using low ranked predicted contacts as non-contacts and adding them as additional restraints, can increase the reconstruction accuracy by 5% when the reconstructed models are evaluated using TM-score.ConclusionsOur findings suggest that secondary structures are invaluable companions of contacts for accurate reconstruction. Confirming some earlier findings, we also find that larger distance thresholds are useful for folding many protein structures which cannot be folded using the standard definition of contacts. Our findings also suggest that for more accurate reconstruction using predicted contacts it is useful to predict contacts at higher distance thresholds (beyond 8 Å) and predict non-contacts.
Highlights
Residue-residue contacts are key features for accurate de novo protein structure prediction
In the context of reconstruction studies being useful for de novo protein structure prediction, they have some limitations. These studies use complete contact maps to reconstruct protein structures, whereas, recent practice for most model building methods has been to use much lesser predicted contacts. These reconstruction studies do not comply with the widelyused contact definition, i.e., the Critical Assessment of Protein Structure Prediction’s (CASP) definition of contacts where 8 Å distance threshold is used with minimum sequence separation of 6 residues
Since secondary structure prediction has reached an accuracy higher than 80% [7, 8], it is meaningful to study how the knowledge of secondary structures can influence the quality of reconstructed models
Summary
Residue-residue contacts are key features for accurate de novo protein structure prediction. In the context of reconstruction studies being useful for de novo protein structure prediction, they have some limitations These studies use complete contact maps to reconstruct protein structures, whereas, recent practice for most model building methods has been to use much lesser predicted contacts. These reconstruction studies do not comply with the widelyused contact definition, i.e., the Critical Assessment of Protein Structure Prediction’s (CASP) definition of contacts where 8 Å distance threshold is used with minimum sequence separation of 6 residues. Since secondary structure prediction has reached an accuracy higher than 80% [7, 8], it is meaningful to study how the knowledge of secondary structures can influence the quality of reconstructed models
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