Adhikari, B. | Search bioRxiv

bioRxiv2017

CONFOLD2: Improved contact-driven ab initio protein structure modeling

BackgroundContact-guided protein structure prediction methods are becoming more and more successful because of the latest advances in residue-residue contact prediction. To support the contact-driven structure prediction, effective tools that can quickly build tertiary structural models of good quality from predicted contacts need to be developed.\n\nResultsWe develop an improved contact-driven protein modeling method, CONFOLD2, and study how it may be effectively used for ab initio protein structure prediction with predicted contacts as input. It builds models using various subsets of input contacts to explore the fold space under the guidance of a soft square energy function, and then clusters the models to obtain top five models. CONFOLD2 is benchmarked on various datasets including CASP11 and 12 datasets with publicly available predicted contacts and yields better performance than the popular CONFOLD method.\n\nConclusionCONFOLD2 allows to quickly generate top five structural models for a protein sequence, when its secondary structures and contacts predictions at hand. CONFOLD2 is publicly available at https://github.com/multicom-toolbox/CONFOLD2/.

bioinformatics↗

bioRxiv2017

DNCON2: Improved protein contact prediction using two-level deep convolutional neural networks

MotivationSignificant improvements in the prediction of protein residue-residue contacts are observed in the recent years. These contacts, predicted using a variety of coevolution-based and machine learning methods, are the key contributors to the recent progress in ab initio protein structure prediction, as demonstrated in the recent CASP experiments. Continuing the development of new methods to reliably predict contact maps is essential to further improve ab initio structure prediction.\n\nResultsIn this paper we discuss DNCON2, an improved protein contact map predictor based on two-level deep convolutional neural networks. It consists of six convolutional neural networks - the first five predict contacts at 6, 7.5, 8, 8.5, and 10 [A] distance thresholds, and the last one uses these five predictions as additional features to predict final contact maps. On the free-modeling datasets in CASP10, 11, and 12 experiments, DNCON2 achieves mean precisions of 35%, 50%, and 53.4%, respectively, higher than 30.6% by MetaPSICOV on CASP10 dataset, 34% by MetaPSICOV on CASP11 dataset, and 46.3% by Raptor-X on CASP12 dataset, when top L/5 long-range contacts are evaluated. We attribute the improved performance of DNCON2 to the inclusion of short- and medium-range contacts into training, two-level approach to prediction, use of the state-of-the-art optimization and activation functions, and a novel deep learning architecture that allows each filter in a convolutional layer to access all the input features of a protein of arbitrary length.\n\nAvailabilityThe web server of DNCON2 is at http://sysbio.rnet.missouri.edu/dncon2/ where training and testing datasets as well as the predictions for CASP10, 11, and 12 free-modeling datasets can also be downloaded. Its source code is available at https://github.com/multicom-toolbox/DNCON2/.\n\nContactchengji@missouri.edu\n\nSupplementary informationSupplementary data are available online.

bioinformatics↗