Dataset Information

Classifying kinase conformations using a machine learning approach.

ABSTRACT: Signaling proteins such as protein kinases adopt a diverse array of conformations to respond to regulatory signals in signaling pathways. Perhaps the most fundamental conformational change of a kinase is the transition between active and inactive states, and defining the conformational features associated with kinase activation is critical for selectively targeting abnormally regulated kinases in diseases. While manual examination of crystal structures have led to the identification of key structural features associated with kinase activation, the large number of kinase crystal structures (~3,500) and extensive conformational diversity displayed by the protein kinase superfamily poses unique challenges in fully defining the conformational features associated with kinase activation. Although some computational approaches have been proposed, they are typically based on a small subset of crystal structures using measurements biased towards the active site geometry.We utilize an unbiased informatics based machine learning approach to classify all eukaryotic protein kinase conformations deposited in the PDB. We show that the orientation of the activation segment, measured by ?, ?, ?1, and pseudo-dihedral angles more accurately classify kinase crystal conformations than existing methods. We show that the formation of the K-E salt bridge is statistically dependent upon the activation segment orientation and identify evolutionary differences between the activation segment conformation of tyrosine and serine/threonine kinases. We provide evidence that our method can identify conformational changes associated with the binding of allosteric regulatory proteins, and show that the greatest variation in inactive structures comes from kinase group and family specific side chain orientations.We have provided the first comprehensive machine learning based classification of protein kinase active/inactive conformations, taking into account more structures and measurements than any previous classification effort. Further, our unbiased classification of inactive structures reveals residues associated with kinase functional specificity. To enable classification of new crystal structures, we have made our classifier publicly accessible through a stand-alone program housed at https://github.com/esbg/kinconform [DOI: 10.5281/zenodo.249090 ].

SUBMITTER: McSkimming DI

PROVIDER: S-EPMC5290640 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Classifying kinase conformations using a machine learning approach.

McSkimming Daniel Ian DI Rasheed Khaled K Kannan Natarajan N

BMC bioinformatics 20170202 1

<h4>Background</h4>Signaling proteins such as protein kinases adopt a diverse array of conformations to respond to regulatory signals in signaling pathways. Perhaps the most fundamental conformational change of a kinase is the transition between active and inactive states, and defining the conformational features associated with kinase activation is critical for selectively targeting abnormally regulated kinases in diseases. While manual examination of crystal structures have led to the identifi ...[more]

PMID: 28152981

Similar Datasets

Project description:Background and objectiveSmoking is the largest preventable cause of death and diseases in the developed world, and advances in modern electronics and machine learning can help us deliver real-time intervention to smokers in novel ways. In this paper, we examine different machine learning approaches to use situational features associated with having or not having urges to smoke during a quit attempt in order to accurately classify high-urge states.MethodsTo test our machine learning approaches, specifically, Bayes, discriminant analysis and decision tree learning methods, we used a dataset collected from over 300 participants who had initiated a quit attempt. The three classification approaches are evaluated observing sensitivity, specificity, accuracy and precision.ResultsThe outcome of the analysis showed that algorithms based on feature selection make it possible to obtain high classification rates with only a few features selected from the entire dataset. The classification tree method outperformed the naive Bayes and discriminant analysis methods, with an accuracy of the classifications up to 86%. These numbers suggest that machine learning may be a suitable approach to deal with smoking cessation matters, and to predict smoking urges, outlining a potential use for mobile health applications.ConclusionsIn conclusion, machine learning classifiers can help identify smoking situations, and the search for the best features and classifier parameters significantly improves the algorithms' performance. In addition, this study also supports the usefulness of new technologies in improving the effect of smoking cessation interventions, the management of time and patients by therapists, and thus the optimization of available health care resources. Future studies should focus on providing more adaptive and personalized support to people who really need it, in a minimum amount of time by developing novel expert systems capable of delivering real-time interventions.

Dataset Information

Classifying kinase conformations using a machine learning approach.

Publications

Classifying kinase conformations using a machine learning approach.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets