caa a22 4500 467938555 CHVBK 20180406153005.0 cr unu---uuuuu 170328e20060101xx s 000 0 eng 10.1007/s10822-006-9035-5 doi (NATIONALLICENCE)springer-10.1007/s10822-006-9035-5 Genetic algorithms as a tool for helix design - computational and experimental studies on prion protein helix 1 [Elektronische Daten] [Jan Ziegler, Stephan Schwarzinger] Summary: Evolutionary computing is a general optimization mechanism successfully implemented for a variety of numeric problems in a variety of fields, including structural biology. We here present an evolutionary approach to optimize helix stability in peptides and proteins employing the AGADIR energy function for helix stability as scoring function. With the ability to apply masks determining positions, which are to remain constant or fixed to a certain class of amino acids, our algorithm is capable of developing stable helical scaffolds containing a wide variety of structural and functional amino acid patterns. The algorithm showed good convergence behaviour in all tested cases and can be parameterized in a wide variety of ways. We have applied our algorithm for the optimization of the stability of prion protein helix 1, a structural element of the prion protein which is thought to play a crucial role in the conformational transition from the cellular to the pathogenic form of the prion protein, and which therefore poses an interesting target for pharmacological as well as genetic engineering approaches to counter the as of yet uncurable prion diseases. NMR spectroscopic investigations of selected stabilizing and destabilizing mutations found by our algorithm could demonstrate its ability to create stabilized variants of secondary structure elements. Springer Science+Business Media, Inc., 2006 amyloidogenic proteins nationallicence genetic algorithms nationallicence helix propensity nationallicence prion protein nationallicence protein design nationallicence protein stabilization nationallicence Ziegler Jan Lehrstuhl Biopolymere, University of Bayreuth, Universitätsstr. 30, 95444, Bayreuth, Germany aut Schwarzinger Stephan Lehrstuhl Biopolymere, University of Bayreuth, Universitätsstr. 30, 95444, Bayreuth, Germany aut Journal of Computer-Aided Molecular Design Springer Netherlands 20/1(2006-01-01), 47-54 0920-654X 20:1<47 2006 20 10822 https://doi.org/10.1007/s10822-006-9035-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10822-006-9035-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ziegler Jan Lehrstuhl Biopolymere, University of Bayreuth, Universitätsstr. 30, 95444, Bayreuth, Germany aut NATIONALLICENCE 700 1- Schwarzinger Stephan Lehrstuhl Biopolymere, University of Bayreuth, Universitätsstr. 30, 95444, Bayreuth, Germany aut NATIONALLICENCE 773 0- Journal of Computer-Aided Molecular Design Springer Netherlands 20/1(2006-01-01), 47-54 0920-654X 20:1<47 2006 20 10822 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer