165 Protein domains: a thermodynamic definition |
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| Authors: | Lauren L. Porter |
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| Affiliation: | 1. Department of Biophysics , Johns Hopkins University , 3400 N. Charles Street, Baltimore , MD , 21218 , USA Phone: Phone: +1 410-516-7244 Fax: Phone: +1 410-516-7244;2. Potomac Affinity Proteins , Institute for Bioscience and Biotechnology Research , 9600 Gudelsky Dr, Rockville , MD , 20850 , USA |
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| Abstract: | Protein domains are conspicuous structural units in globular proteins, and their identification has been a topic of intense biochemical interest dating back to the earlier crystal structures. Numerous disparate domain identification algorithms have been proposed, all involving some combination of visual intuition and/or structure-based decomposition. Instead, we present a rigorous thermodynamically based approach that redefines domains as cooperative chain segments. In greater detail, most small proteins fold with high cooperativity, meaning that the equilibrium population is dominated by completely folded and unfolded molecules, with a negligible subpopulation of partially folded intermediates. Here, domains are equated to chain segments that retain full cooperativity when excised from their parent structures. Implementing this approach computationally, the domains in a large representative set of proteins were identified; all exhibit consistency with experimental findings. Our reframed interpretation of a protein domain transforms an indeterminate structural phenomenon into a quantifiable molecular property, grounded in solution thermodynamics. |
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