Knowledge-based potential for positioning membrane-associated structures and assessing residue-specific energetic contributions.
Structure
; 20(5): 924-35, 2012 May 09.
Article
en 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas
/
Proteínas de la Membrana
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Año:
2012
Tipo del documento:
Article