Model-building codes for membrane proteins.

Shirley, David Noyes ; Hunt, Thomas W. ; Brown, W. Michael ; Schoeniger, Joseph S. (Sandia National Laboratories, Livermore, CA) ; Slepoy, Alexander ; Sale, Kenneth L. (Sandia National Laboratories, Livermore, CA) ; Young, Malin M. (Sandia National Laboratories, Livermore, CA) ; Faulon, Jean-Loup Michel ; Gray, Genetha Anne (Sandia National Laboratories, Livermore, CA)

Sandia National Laboratories

关键词: Membrane Proteins;    Amino Acids;    Membrane Proteins.;    Crystal Structure;    36 Materials Science;   

DOI  :  10.2172/920776
RP-ID  :  SAND2004-6383
RP-ID  :  AC04-94AL85000
RP-ID  :  920776

美国|英语

来源: UNT Digital Library

【 摘 要 】

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.