Dataset Information

Integrating co-evolutionary signals and other properties of residue pairs to distinguish biological interfaces from crystal contacts.

ABSTRACT: It remains challenging to accurately discriminate between biological and crystal interfaces. Most existing analyses and algorithms focused on the features derived from a single side of the interface. However, less attention has been paid to the properties of residue pairs across protein interfaces. To address this problem, we defined a novel co-evolutionary feature for homodimers through integrating direct coupling analysis and image processing techniques. The residue pairs across biological homodimeric interfaces were significantly enriched in co-evolving residues compared to those across crystal contacts, resulting in a promising classification accuracy with area under the curves (AUCs) of >0.85. Considering the availability of co-evolutionary feature, we also designed other residue pair based features that were useful for both homodimers and heterodimers. The most informative residue pairs were identified to reflect the interaction preferences across protein interfaces. Regarding the other extant properties, we designed the new descriptors at the interface residue level as well as at the pairwise contact level. Extensive validation showed that these single properties can be used to identify biological interfaces with AUCs ranging from 0.60 to 0.88. By integrating co-evolutionary feature with other residue pair based properties, our final prediction model output excellent performance with AUCs of >0.91 on different datasets. Compared to existing methods, our algorithm not only yielded better or comparable results but also provided complementary information. An easy-to-use web server is freely accessible at http://liulab.hzau.edu.cn/RPAIAnalyst.

SUBMITTER: Hu J

PROVIDER: S-EPMC6194302 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Integrating co-evolutionary signals and other properties of residue pairs to distinguish biological interfaces from crystal contacts.

Hu Jian J Liu Hui-Fang HF Sun Jun J Wang Jia J Liu Rong R

Protein science : a publication of the Protein Society 20180810 9

It remains challenging to accurately discriminate between biological and crystal interfaces. Most existing analyses and algorithms focused on the features derived from a single side of the interface. However, less attention has been paid to the properties of residue pairs across protein interfaces. To address this problem, we defined a novel co-evolutionary feature for homodimers through integrating direct coupling analysis and image processing techniques. The residue pairs across biological hom ...[more]

PMID: 29931702

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Project description:BackgroundDistinction between true protein interactions and crystal packing contacts is important for structural bioinformatics studies to respond to the need of accurate classification of the rapidly increasing protein structures. There are many unannotated crystal contacts and there also exist false annotations in this rapidly expanding volume of data. Previous tools have been proposed to address this problem. However, challenging issues still remain, such as low performance when the training and test data contain mixed interfaces having diverse sizes of contact areas.Methods and resultsB factor is a measure to quantify the vibrational motion of an atom, a more relevant feature than interface size to characterize protein binding. We propose to use three features related to B factor for the classification between biological interfaces and crystal packing contacts. The first feature is the sum of the normalized B factors of the interfacial atoms in the contact area, the second is the average of the interfacial B factor per residue in the chain, and the third is the average number of interfacial atoms with a negative normalized B factor per residue in the chain. We investigate the distribution properties of these basic features and a compound feature on four datasets of biological binding and crystal packing, and on a protein binding-only dataset with known binding affinity. We also compare the cross-dataset classification performance of these features with existing methods and with a widely-used and the most effective feature interface area. The results demonstrate that our features outperform the interface area approach and the existing prediction methods remarkably for many tests on all of these datasets.ConclusionsThe proposed B factor related features are more effective than interface area to distinguish crystal packing from biological binding interfaces. Our computational methods have a potential for large-scale and accurate identification of biological interactions from the experimentally determined structural data stored at PDB which may have diverse interface sizes.

Dataset Information

Integrating co-evolutionary signals and other properties of residue pairs to distinguish biological interfaces from crystal contacts.

Publications

Integrating co-evolutionary signals and other properties of residue pairs to distinguish biological interfaces from crystal contacts.

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