This Article Full Text Full Text (PDF) Supplemental All Versions of this Article: biophysj.105.074401v1 90/8/2745    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 Fuchs, P. F. J. Articles by Tamburro, A. M. Search for Related Content PubMed PubMed Citation Articles by Fuchs, P. F. J. Articles by Tamburro, A. M.

Kinetics and Thermodynamics of Type VIII ß-Turn Formation: A CD, NMR, and Microsecond Explicit Molecular Dynamics Study of the GDNP Tetrapeptide

Patrick F. J. Fuchs ^*, Alexandre M. J. J. Bonvin , Brigida Bochicchio , Antonietta Pepe , Alain J. P. Alix  and Antonio M. Tamburro 

^* Equipe de Bioinformatique Génomique et Moléculaire, INSERM U726, Université Paris 7, 75251 Paris Cedex 05, France; Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CH Utrecht, The Netherlands; Dipartimento di Chimica, Università degli Studi della Basilicata, 85100 Potenza, Italy; and Laboratoire de Spectroscopies et Structures BioMoléculaires, Université de Reims Champagne-Ardenne, Faculté des Sciences, BP 1039, 51687 Reims Cedex 2, France

Correspondence: Address reprint requests to Alexandre M. J. J. Bonvin, E-mail: a.m.j.j.bonvin{at}chem.uu.nl; or Antonio M. Tamburro, E-mail: tamburro{at}unibas.it.

We report an experimental and theoretical study on type VIII ß-turn using a designed peptide of sequence GDNP. CD and NMR studies reveal that this peptide exists in equilibrium between type VIII ß-turn and extended conformations. Extensive MD simulations give a description of the free energy landscape of the peptide in which we retrieve the same two main conformations suggested by the experiments. The free energy difference between the two conformational states is very small and the transition between them occurs within a few kT at 300 K on a nanosecond timescale. The equilibrium is mainly driven by entropic contribution, which favors extended conformations over ß-turns. This confirms other theoretical studies showing that ß-turns are marginally stable in water solution because of the larger entropy of the extended state unless some stabilizing interactions exist. Our observations may be extended to any type of ß-turn and have important consequences for protein folding. A comparison of our MD and CD results also suggests a possible type VIII ß-turn CD signature indicated by one main band at 200 nm, close to that of random coil, and a fairly large shoulder at 220 nm. Last, our results clearly show that the XXXP motif can only fold into a type VIII ß-turn, which is consistent with its fairly strong propensity for this type of turn. This important finding may help for peptide design and is in line with recent studies on bioactive elastin peptides.