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Knowledge-based potential for positioning membrane-associated structures and assessing residue-specific energetic contributions.
Schramm, Chaim A; Hannigan, Brett T; Donald, Jason E; Keasar, Chen; Saven, Jeffrey G; Degrado, William F; Samish, Ilan.
Afiliação
  • Schramm CA; Graduate Group in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Structure ; 20(5): 924-35, 2012 May 09.
Article em En | MEDLINE | ID: mdl-22579257
ABSTRACT
The complex hydrophobic and hydrophilic milieus of membrane-associated proteins pose experimental and theoretical challenges to their understanding. Here, we produce a nonredundant database to compute knowledge-based asymmetric cross-membrane potentials from the per-residue distributions of C(ß), C(γ) and functional group atoms. We predict transmembrane and peripherally associated regions from genomic sequence and position peptides and protein structures relative to the bilayer (available at http//www.degradolab.org/ez). The pseudo-energy topological landscapes underscore positional stability and functional mechanisms demonstrated here for antimicrobial peptides, transmembrane proteins, and viral fusion proteins. Moreover, experimental effects of point mutations on the relative ratio changes of dual-topology proteins are quantitatively reproduced. The functional group potential and the membrane-exposed residues display the largest energetic changes enabling to detect native-like structures from decoys. Hence, focusing on the uniqueness of membrane-associated proteins and peptides, we quantitatively parameterize their cross-membrane propensity, thus facilitating structural refinement, characterization, prediction, and design.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas / Proteínas de Membrana Idioma: En Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas / Proteínas de Membrana Idioma: En Ano de publicação: 2012 Tipo de documento: Article