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Structure-Functional Prediction and Analysis of Cancer Mutation Effects in Protein Kinases
Joint Authors
Dixit, Anshuman
Verkhivker, Gennady M.
Source
Computational and Mathematical Methods in Medicine
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-24, 24 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-04-08
Country of Publication
Egypt
No. of Pages
24
Main Subjects
Abstract EN
A central goal of cancer research is to discover and characterize the functional effects of mutated genes that contribute to tumorigenesis.
In this study, we provide a detailed structural classification and analysis of functional dynamics for members of protein kinase families that are known to harbor cancer mutations.
We also present a systematic computational analysis that combines sequence and structure-based prediction models to characterize the effect of cancer mutations in protein kinases.
We focus on the differential effects of activating point mutations that increase protein kinase activity and kinase-inactivating mutations that decrease activity.
Mapping of cancer mutations onto the conformational mobility profiles of known crystal structures demonstrated that activating mutations could reduce a steric barrier for the movement from the basal “low” activity state to the “active” state.
According to our analysis, the mechanism of activating mutations reflects a combined effect of partial destabilization of the kinase in its inactive state and a concomitant stabilization of its active-like form, which is likely to drive tumorigenesis at some level.
Ultimately, the analysis of the evolutionary and structural features of the major cancer-causing mutational hotspot in kinases can also aid in the correlation of kinase mutation effects with clinical outcomes.
American Psychological Association (APA)
Dixit, Anshuman& Verkhivker, Gennady M.. 2014. Structure-Functional Prediction and Analysis of Cancer Mutation Effects in Protein Kinases. Computational and Mathematical Methods in Medicine،Vol. 2014, no. 2014, pp.1-24.
https://search.emarefa.net/detail/BIM-488533
Modern Language Association (MLA)
Dixit, Anshuman& Verkhivker, Gennady M.. Structure-Functional Prediction and Analysis of Cancer Mutation Effects in Protein Kinases. Computational and Mathematical Methods in Medicine No. 2014 (2014), pp.1-24.
https://search.emarefa.net/detail/BIM-488533
American Medical Association (AMA)
Dixit, Anshuman& Verkhivker, Gennady M.. Structure-Functional Prediction and Analysis of Cancer Mutation Effects in Protein Kinases. Computational and Mathematical Methods in Medicine. 2014. Vol. 2014, no. 2014, pp.1-24.
https://search.emarefa.net/detail/BIM-488533
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-488533