Computational Design of a Single Amino Acid Sequence that Can Switch between Two Distinct Protein Folds.

@article{citeulike:485372, abstract = {The functions of many proteins are mediated by specific conformational changes, and therefore the ability to design primary sequences capable of secondary and tertiary changes is an important step toward the creation of novel functional proteins. To this end, we have developed an algorithm that can optimize a single amino acid sequence for multiple target structures. The algorithm consists of an outer loop, in which sequence space is sampled by a Monte Carlo search with simulated annealing, and an inner loop, in which the effect of a given mutation is evaluated on the various target structures by using the rotamer packing routine and composite energy function of the protein design software, RosettaDesign. We have experimentally tested the method by designing a peptide, Sw2, which can be switched from a 2Cys-2His zinc finger-like fold to a trimeric coiled-coil fold, depending upon the pH or the presence of transition metals. Physical characterization of Sw2 confirms that it is able to reversibly adopt each intended target fold.}, address = {Contribution from the Department of Biochemistry and Biophysics, University of North Carolina, Campus Box 7260, Chapel Hill, North Carolina 27599.}, author = {Ambroggio, X. I. and Kuhlman, B. }, citeulike-article-id = {485372}, doi = {http://dx.doi.org/10.1021/ja054718w}, issn = {0002-7863}, journal = {J Am Chem Soc}, keywords = {protein\_design, protein\_dynamics, protein\_sequence, protein\_structure}, month = {February}, number = {4}, pages = {1154--1161}, posted-at = {2007-09-04 19:32:05}, priority = {2}, title = {Computational Design of a Single Amino Acid Sequence that Can Switch between Two Distinct Protein Folds.}, url = {http://dx.doi.org/10.1021/ja054718w}, volume = {128}, year = {2006} }

TY - JOUR ID - citeulike:485372 L3 - citeulike-article-id:485372 TI - Computational Design of a Single Amino Acid Sequence that Can Switch between Two Distinct Protein Folds. JF - J Am Chem Soc VL - 128 IS - 4 SP - 1154 EP - 1161 AD - Contribution from the Department of Biochemistry and Biophysics, University of North Carolina, Campus Box 7260, Chapel Hill, North Carolina 27599. SN - 0002-7863 N2 - The functions of many proteins are mediated by specific conformational changes, and therefore the ability to design primary sequences capable of secondary and tertiary changes is an important step toward the creation of novel functional proteins. To this end, we have developed an algorithm that can optimize a single amino acid sequence for multiple target structures. The algorithm consists of an outer loop, in which sequence space is sampled by a Monte Carlo search with simulated annealing, and an inner loop, in which the effect of a given mutation is evaluated on the various target structures by using the rotamer packing routine and composite energy function of the protein design software, RosettaDesign. We have experimentally tested the method by designing a peptide, Sw2, which can be switched from a 2Cys-2His zinc finger-like fold to a trimeric coiled-coil fold, depending upon the pH or the presence of transition metals. Physical characterization of Sw2 confirms that it is able to reversibly adopt each intended target fold. KW - protein_design KW - protein_dynamics KW - protein_sequence KW - protein_structure AU - Ambroggio, XI AU - Kuhlman, B PY - 2006/02/01/ UR - http://dx.doi.org/10.1021/ja054718w ER -