DOI: 10.1073/pnas.95.21.12179. Peptide design by artificial neural networks and computer-based evolutionary search

Peptide design by artificial neural networks and computer-based evolutionary search

10.1073/pnas.95.21.12179

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

A technique for systematic peptide variation by a combination of rational and evolutionary approaches is presented. The design scheme consists of five consecutive steps: ( i ) identification of a “seed peptide” with a desired activity, ( ii ) generation of variants selected from a physicochemical space around the seed peptide, ( iii ) synthesis and testing of this biased library, ( iv ) modeling of a quantitative sequence-activity relationship by an artificial neural network, and ( v ) de novo design by a computer-based evolutionary search in sequence space using the trained neural network as the fitness function. This strategy was successfully applied to the identification of novel peptides that fully prevent the positive chronotropic effect of anti-β 1 -adrenoreceptor autoantibodies from the serum of patients with dilated cardiomyopathy. The seed peptide, comprising 10 residues, was derived by epitope mapping from an extracellular loop of human β 1 -adrenoreceptor. A set of 90 peptides was synthesized and tested to provide training data for neural network development. De novo design revealed peptides with desired activities that do not match the seed peptide sequence. These results demonstrate that computer-based evolutionary searches can generate novel peptides with substantial biological activity.

Bibliography

Schneider, G., SchrÃ¶dl, W., Wallukat, G., MÃ¼ller, J., Nissen, E., RÃ¶nspeck, W., Wrede, P., & Kunze, R. (1998). Peptide design by artificial neural networks and computer-based evolutionary search. Proceedings of the National Academy of Sciences, 95(21), 12179â12184.

Authors 8

Gisbert Schneider (first)
Wieland Schrödl (additional)
Gerd Wallukat (additional)
Johannes Müller (additional)
Eberhard Nissen (additional)
Wolfgang Rönspeck (additional)
Paul Wrede (additional)
Rudolf Kunze (additional)

References 33 Referenced 69

10.1016/0168-1656(94)90039-6
10.1515/9783110808902
10.1146/annurev.biophys.26.1.27
G Schneider, H-P Grunert, J Schuchhardt, K U Wolf, G Müller, K-O Habermehl, H Zeichhardt, P Wrede Min Invas Med 6, 106–115 (1995). / Min Invas Med by Schneider G (1995)
10.1007/BF00201426
10.1016/S0006-3495(94)80782-9
10.1016/S0006-3495(95)80205-5
10.1161/01.RES.64.1.97
10.1161/01.CIR.89.6.2760
10.3109/07853899509031954
G Wallukat, A Wollenberger Biomed Biochim Acta 78, 634–639 (1987). / Biomed Biochim Acta by Wallukat G (1987)
10.1016/S0022-2828(08)80036-3
10.1073/pnas.81.13.3998
10.1016/0022-1759(87)90085-8
10.1089/aid.1990.6.943
10.1089/aid.1992.8.1301
10.1021/ja00897a025
E Atherton, R C Sheppard Solid Phase Peptide Synthesis, a Practical Approach (IRL, Oxford, 1989). / Solid Phase Peptide Synthesis, a Practical Approach by Atherton E (1989)
P Henklein, M Beyermann, M Bienert, R Knorr Peptide 1990, Proceedings of the 21st European Peptide Symposium, eds E Giralt, D Andreu (ESCOM, Leiden), pp. 67–68 (1990). / Peptide 1990, Proceedings of the 21st European Peptide Symposium by Henklein P (1990)
A Wollenberger, G Wallukat Biomed Biochim Acta 42, 917–929 (1983). / Biomed Biochim Acta by Wollenberger A (1983)
10.1016/S0002-9149(70)80006-6
B W Kernighan, D M Ritchie The C Programming Language (Prentice–Hall, Englewood Cliffs, NJ, 1988). / The C Programming Language by Kernighan B W (1988)
10.1146/annurev.bb.15.060186.001541
10.1016/S0969-2126(00)00065-4
10.1021/j100335a010
10.1007/978-1-4757-1904-8
10.1109/T-C.1969.222678
10.1016/S0263-7855(97)00078-7
10.1016/S0079-6107(98)00026-1
10.1016/S0092-8674(00)80468-7
10.1016/B978-012213815-7/50002-9
10.1007/BF00556363
10.1126/science.2888192

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:31 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 4:59 p.m.)
Indexed	2 months, 4 weeks ago (June 5, 2025, 8:05 a.m.)
Issued	26 years, 10 months ago (Oct. 13, 1998)
Published	26 years, 10 months ago (Oct. 13, 1998)
Published Online	26 years, 10 months ago (Oct. 13, 1998)
Published Print	26 years, 10 months ago (Oct. 13, 1998)

Funders 0

None

BibTeX

@article{Schneider_1998, title={Peptide design by artificial neural networks and computer-based evolutionary search}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.21.12179}, DOI={10.1073/pnas.95.21.12179}, number={21}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Schneider, Gisbert and Schrödl, Wieland and Wallukat, Gerd and Müller, Johannes and Nissen, Eberhard and Rönspeck, Wolfgang and Wrede, Paul and Kunze, Rudolf}, year={1998}, month=oct, pages={12179–12184} }

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