Optimal contact definition for reconstruction of Contact Maps

By Jose M. Duarte, Rajagopal Sathyapriya, Henning Stehr, Ioannis Filippis, Michael Lappe. 2010

75 citations recorded by the source corpus.

BackgroundContact maps have been extensively used as a simplified representation of protein structures. They capture most important features of a protein's fold, being preferred by a number of researchers for the description and study of protein structures. Inspired by the model's simplicity many groups have dedicated a considerable amount of effort towards contact prediction as a proxy for protein structure prediction. However a contact map's biological interest is subject to the availability of reliable methods for the 3-dimensional reconstruction of the structure.ResultsWe use an implementation of the well-known distance geometry protocol to build realistic protein 3-dimensional models from contact maps, performing an extensive exploration of many of the parameters involved in the reconstruction process. We try to address the questions: a) to what accuracy does a contact map represent its corresponding 3D structure, b) what is the best contact map representation with regard to reconstructability and c) what is the effect of partial or inaccurate contact information on the 3D structure recovery. Our results suggest that contact maps derived from the application of a distance cutoff of 9 to 11Å around the Cβatoms constitute the most accurate representation of the 3D structure. The reconstruction process does not provide a single solution to the problem but rather an ensemble of conformations that are within 2Å RMSD of the crystal structure and with lower values for the pairwise average ensemble RMSD. Interestingly it is still possible to recover a structure with partial contact information, although wrong contacts can lead to dramatic loss in reconstruction fidelity.ConclusionsThus contact maps represent a valid approximation to the structures with an accuracy comparable to that of experimental methods. The optimal contact definitions constitute key guidelines for methods based on contact maps such as structure prediction through contacts and structural alignments based on maximum contact map overlap.

Subfields: Atomic and Molecular Physics, and Optics, Materials Chemistry, Molecular Biology

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Citations in the corpus

Protein 3D Structure Computed from Evolutionary Sequence Variation (2011, background): “This number is close to those reported by other groups, who used fully correct close residue pairs to impose inexact distances as constraints [50,51,67].”
ConEVA: a toolbox for comprehensive assessment of protein contacts (2016, background): “…experiments on true contact reconstruction have suggested that 9 Å or more distance threshold delivers best reconstruction with C β atom [10, 11], but the Critical Assessment of Protein Structure Prediction (CASP) ’ s definition of 8 Å threshold is still widely used to predict contacts [1 –…”
CONFOLD: Residue-Residue Contact-guided ab initio Protein Folding (2015, methodology): “In contrast, the models reconstructed by CNS DGSA and Reconstruct have good global topology but poor secondary structures, whereas the model reconstructed by Mod-eler has poor global topology but better secondary structures.”
3D Protein Structure Predicted from Sequence (2011, unknown): “Others have shown that given sufficient correct (true positive) contacts combined with a lack of incorrect (false positive) contacts, predicted contacts can be implemented as residue-‐residue distance restraints to ”