This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.106.097550v1 92/8/2904    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 Makowska, J. Articles by Scheraga, H. A. Search for Related Content PubMed PubMed Citation Articles by Makowska, J. Articles by Scheraga, H. A.

Further Evidence for the Absence of Polyproline II Stretch in the XAO Peptide

Joanna Makowska ^* , Sylwia Rodziewicz-Motowido ^* , Katarzyna Bagiska ^*, Mariusz Makowski ^* , Jorge A. Vila  , Adam Liwo , Lech Chmurzyski ^* and Harold A. Scheraga 

^* Faculty of Chemistry, University of Gdask, Sobieskiego 18, 80-952 Gdask, Poland; Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853-1301; and Universidad Nacional de San Luis, Facultad de Ciencias Físico Matemáticas y Naturales, Instituto de Matemática Aplicada San Luis, Consejo Nacional de Investigaciones Científicas y Técnicas, Ejército de los Andes, 950-5700 San Luis, Argentina

Correspondence: Address reprint requests to Harold A. Scheraga, Tel.: 607-255-4034; Fax: 607-254-254 4700; E-mail: has5{at}cornell.edu.

It has been suggested that the alanine-based peptide with sequence Ac-XX-[A]₇-OO-NH₂, termed XAO where X denotes diaminobutyric acid and O denotes ornithine, exists in a predominantly polyproline-helix (P_II) conformation in aqueous solution. In our recent work, we demonstrated that this "polyproline conformation" should be regarded as a set of local conformational states rather than as the overall conformation of the molecule. In this work, we present further evidence to support this statement. Differential scanning calorimetry measurements showed only a very small peak in the heat capacity of an aqueous solution of XAO at 57°C, whereas the suggested transition to the P_II structure should occur at 30°C. We also demonstrate that the temperature dependence of the ³J_HNH coupling constants of the alanine residues can be explained qualitatively in terms of Boltzmann averaging over all local conformational states; therefore, this temperature dependence proves that a conformational transition does not occur. Canonical MD simulations with the solvent represented by the generalized Born model, and with time-averaged NMR-derived restraints, demonstrate the presence of an ensemble of structures with a substantial amount of local P_II conformational states but not with an overall P_II conformation.