Model-building codes for membrane proteins.

Technical Report · Sat Jan 01 04:00:00 EST 2005

DOI:https://doi.org/10.2172/920776· OSTI ID:920776

Shirley, David Noyes; Hunt, Thomas W; Brown, W Michael; Schoeniger, Joseph S ^[1]; Slepoy, Alexander; Sale, Kenneth L ^[1]; Young, Malin M ^[1]; Faulon, Jean-Loup Michel; Gray, Genetha Anne ^[1]

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1. Sandia National Laboratories, Livermore, CA

We have developed a novel approach to modeling the transmembrane spanning helical bundles of integral membrane proteins using only a sparse set of distance constraints, such as those derived from MS3-D, dipolar-EPR and FRET experiments. Algorithms have been written for searching the conformational space of membrane protein folds matching the set of distance constraints, which provides initial structures for local conformational searches. Local conformation search is achieved by optimizing these candidates against a custom penalty function that incorporates both measures derived from statistical analysis of solved membrane protein structures and distance constraints obtained from experiments. This results in refined helical bundles to which the interhelical loops and amino acid side-chains are added. Using a set of only 27 distance constraints extracted from the literature, our methods successfully recover the structure of dark-adapted rhodopsin to within 3.2 {angstrom} of the crystal structure.

• Research Organization: Sandia National Laboratories
• Sponsoring Organization: USDOE
• DOE Contract Number: AC04-94AL85000
• OSTI ID: 920776
• Report Number(s): SAND2004-6383
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
ALGORITHMS
AMINO ACIDS
Biological models.
CRYSTAL STRUCTURE
MEMBRANE PROTEINS
Membrane proteins.
Models
Biological.
RHODOPSIN
SIMULATION