Albany 2013: Book of Abstracts

category image Albany 2013
Conversation 18
June 11-15 2013
©Adenine Press (2012)

Protein Domains - A thermodynamic definition

Protein domains are conspicuous structural units in globular proteins, and their identification has been a topic of intense biochemical interest dating back to the earliest 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 completely 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.

Lauren L. Porter1
George D. Rose

T.C. Jenkins Department of Biophysics
Johns Hopkins University
3400 N. Charles Street
Baltimore, MD 21218, U.S.A.

phone: 410-516-7244
fax: 410-516-4118

1Current address:
Potomac Affinity Proteins
Institute for Bioscience and Biotechnology Research
9600 Gudelsky Dr.
Rockville, MD 20850