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A tetrapeptide fragment‐based design method results in highly stable artificial proteins
Author(s) -
Dallüge Roman,
Oschmann Jan,
Birkenmeier Olaf,
Lücke Christian,
Lilie Hauke,
Rudolph Rainer,
Lange Christian
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21493
Subject(s) - tetrapeptide , circular dichroism , folding (dsp implementation) , protein design , protein tertiary structure , protein folding , chemistry , fragment (logic) , protein secondary structure , protein structure , computational biology , computer science , crystallography , algorithm , peptide , biology , biochemistry , engineering , electrical engineering
Computational protein design has progressed rapidly over the last years. A number of design methods have been proposed and tested. In this paper, we report the successful application of a fragment‐based method for protein design. The method uses statistical information on tetrapeptide backbone conformations. The previously published artificial fold of TOP 7 (Kuhlman et al., Science, 2003; 302:1364–1368) was chosen as template. A series of polypeptide sequences were created that were predicted to fold into this target structure. Two of the designed proteins, M5 and M7, were expressed and characterized by fluorescence spectroscopy, circular dichroism and NMR. They showed the hallmarks of well‐ordered tertiary structure as well as cooperative folding/unfolding transitions. Furthermore, the two novel proteins were found to be highly stable against temperature and denaturant‐induced unfolding. Proteins 2007. © 2007 Wiley‐Liss, Inc.