This Article Full Text Full Text (PDF) Supplement All Versions of this Article: biophysj.107.113043v1 93/12/4278    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Esteban-Martín, S. Articles by Salgado, J. Search for Related Content PubMed PubMed Citation Articles by Esteban-Martín, S. Articles by Salgado, J.

The Dynamic Orientation of Membrane-Bound Peptides: Bridging Simulations and Experiments

Instituto de Ciencia Molecular (Universitat de València), Paterna (Valencia), Spain

Correspondence: Address reprint requests to Jesús Salgado, Tel.: 34-96-354-3016; E-mail: jesus.salgado{at}uv.es.

The structural organization in a peptide/membrane supramolecular complex is best described by knowledge of the peptide orientation plus its time-dependent and spatial fluctuations. The static orientation, defined by the peptide tilt and a rotation about its molecular axis, is accessible through a number of spectroscopic methods. However, peptide dynamics, although relevant to understand the functionality of these systems, remains largely unexplored. Here, we describe the orientation and dynamics of Trp-flanked and Lys-flanked hydrophobic peptides in a lipid bilayer from molecular dynamics simulations. A novel view is revealed, where collective nontrivial distributions of time-evolving and ensemble peptide orientations closely represent the systems as studied experimentally. Such global distributions are broad and unveil the existence of orientational states, which depend on the anchoring mode of interfacial residues. We show that this dynamics modulates ²H quadrupolar splittings and introduces ambiguity in the analysis of NMR data. These findings demonstrate that structural descriptions of peptide/membrane complexes are incomplete, and in cases even imprecise, without knowledge of dynamics.