Dataset Information

Using inferred residue contacts to distinguish between correct and incorrect protein models.

ABSTRACT:

Motivation

The de novo prediction of 3D protein structure is enjoying a period of dramatic improvements. Often, a remaining difficulty is to select the model closest to the true structure from a group of low-energy candidates. To what extent can inter-residue contact predictions from multiple sequence alignments, information which is orthogonal to that used in most structure prediction algorithms, be used to identify those models most similar to the native protein structure?

Results

We present a Bayesian inference procedure to identify residue pairs that are spatially proximal in a protein structure. The method takes as input a multiple sequence alignment, and outputs an accurate posterior probability of proximity for each residue pair. We exploit a recent metagenomic sequencing project to create large, diverse and informative multiple sequence alignments for a test set of 1656 known protein structures. The method infers spatially proximal residue pairs in this test set with good accuracy: top-ranked predictions achieve an average accuracy of 38% (for an average 21-fold improvement over random predictions) in cross-validation tests. Notably, the accuracy of predicted 3D models generated by a range of structure prediction algorithms strongly correlates with how well the models satisfy probable residue contacts inferred via our method. This correlation allows for confident rejection of incorrect structural models.

Availability

An implementation of the method is freely available at http://www.doe-mbi.ucla.edu/services.

SUBMITTER: Miller CS

PROVIDER: S-EPMC2638260 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Publications

Using inferred residue contacts to distinguish between correct and incorrect protein models.

Miller Christopher S CS Eisenberg David D

Bioinformatics (Oxford, England) 20080529 14

<h4>Motivation</h4>The de novo prediction of 3D protein structure is enjoying a period of dramatic improvements. Often, a remaining difficulty is to select the model closest to the true structure from a group of low-energy candidates. To what extent can inter-residue contact predictions from multiple sequence alignments, information which is orthogonal to that used in most structure prediction algorithms, be used to identify those models most similar to the native protein structure?<h4>Results</ ...[more]

PMID: 18511466

Similar Datasets

Project description:BackgroundThe ability to predict which pairs of amino acid residues in a protein are in contact with each other offers many advantages for various areas of research that focus on proteins. For example, contact prediction can be used to reduce the computational complexity of predicting the structure of proteins and even to help identify functionally important regions of proteins. These predictions are becoming especially important given the relatively low number of experimentally determined protein structures compared to the amount of available protein sequence data.ResultsHere we have developed and benchmarked a set of machine learning methods for performing residue-residue contact prediction, including random forests, direct-coupling analysis, support vector machines, and deep networks (stacked denoising autoencoders). These methods are able to predict contacting residue pairs given only the amino acid sequence of a protein. According to our own evaluations performed at a resolution of +/- two residues, the predictors we trained with the random forest algorithm were our top performing methods with average top 10 prediction accuracy scores of 85.13% (short range), 74.49% (medium range), and 54.49% (long range). Our ensemble models (stacked denoising autoencoders combined with support vector machines) were our best performing deep network predictors and achieved top 10 prediction accuracy scores of 75.51% (short range), 60.26% (medium range), and 43.85% (long range) using the same evaluation. These tests were blindly performed on targets from the CASP11 dataset; and the results suggested that our models achieved comparable performance to contact predictors developed by groups that participated in CASP11.ConclusionsDue to the challenging nature of contact prediction, it is beneficial to develop and benchmark a variety of different prediction methods. Our work has produced useful tools with a simple interface that can provide contact predictions to users without requiring a lengthy installation process. In addition to this, we have released our C++ implementation of the direct-coupling analysis method as a standalone software package. Both this tool and our RFcon web server are freely available to the public at http://dna.cs.miami.edu/RFcon /.

Dataset Information

Using inferred residue contacts to distinguish between correct and incorrect protein models.

Motivation

Results

Availability

Publications

Using inferred residue contacts to distinguish between correct and incorrect protein models.

Similar Datasets

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