title: Multiple loop conformations of peptides predicted by molecular dynamics simulations are compatible with nuclear magnetic resonance.
abstract: The affinity and selectivity of protein-protein interactions can be fine-tuned by varying the size, flexibility, and amino acid composition of involved surface loops. As a model for such surface loops, we study the conformational landscape of an octapeptide, whose flexibility is chemically steered by a covalent ring closure integrating an azobenzene dye into and by a disulfide bridge additionally constraining the peptide backbone. Because the covalently integrated azobenzene dyes can be switched by light between a bent cis state and an elongated trans state, six cyclic peptide models of strongly different flexibilities are obtained. The conformational states of these peptide models are sampled by NMR and by unconstrained molecular dynamics (MD) simulations. Prototypical conformations and the free-energy landscapes in the high-dimensional space spanned by the phi/psi angles at the peptide backbone are obtained by clustering techniques from the MD trajectories. Multiple open-loop conformations are shown to be predicted by MD particularly in the very flexible cases and are shown to comply with the NMR data despite the fact that such open-loop conformations are missing in the refined NMR structures.
authors.affiliation: Lehrstuhl für BioMolekulare Optik, Oettingenstrasse 67, Ludwig-Maximilians-Universität München, 80538 München, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Carstens
authors.forename: Christian
authors.initials: C
authors.lastname: Renner
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Milbradt
authors.forename: Luis
authors.initials: L
authors.lastname: Moroder
authors.forename: Paul
authors.initials: P
authors.lastname: Tavan
mesh_terms: D062365:Aminobenzoates / Q000737:chemistry*; D001391:Azo Compounds / Q000737:chemistry*; D004396:Coloring Agents; D003198:Computer Simulation; D004220:Disulfides / Q000737:chemistry; D007536:Isomerism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010456:Peptides, Cyclic / Q000737:chemistry*; D025341:Principal Component Analysis; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D062366:para-Aminobenzoates
chemical_list: C417554:(4-amino)phenylazobenzoic acid; D062365:Aminobenzoates; D001391:Azo Compounds; D004396:Coloring Agents; D004220:Disulfides; D010456:Peptides, Cyclic; D062366:para-Aminobenzoates