Identification of recurring protein structure microenvironments and discovery of novel functional sites around CYS residues.
Abstract
The emergence of structural genomics presents significant challenges in the annotation of biologically uncharacterized proteins. Unfortunately, our ability to analyze these proteins is restricted by the limited catalog of known molecular functions and their associated 3D motifs. In order to identify novel 3D motifs that may be associated with molecular functions, we employ an unsupervised, two-phase clustering approach that combines k-means and hierarchical clustering with knowledge-informed cluster selection and annotation methods. We applied the approach to approximately 20,000 cysteine-based protein microenvironments (3D regions 7.5 A in radius) and identified 70 interesting clusters, some of which represent known motifs (e.g. metal binding and phosphatase activity), and some of which are novel, including several zinc binding sites. Detailed annotation results are available online for all 70 clusters at http://feature.stanford.edu/clustering/cys. The use of microenvironments instead of backbone geometric criteria enables flexible exploration of protein function space, and detection of recurring motifs that are discontinuous in sequence and diverse in structure. Clustering microenvironments may thus help to functionally chara...Continue Reading
References
The computational analysis of scientific literature to define and recognize gene expression clusters
Citations
Software Mentioned
Related Concepts
Related Feeds
BioHub - Researcher Network
The Chan-Zuckerberg Biohub aims to support the fundamental research and develop the technologies that will enable physicians to cure, prevent, or manage all diseases in our childrens' lifetimes. The CZ Biohub brings together researchers from UC Berkeley, Stanford, and UCSF. Find the latest research from the CZ Biohub researcher network here.