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Simulated Molecular Evolution for Anticancer Peptide Design
Author(s) -
Neuhaus Claudia S.,
Gabernet Gisela,
Steuer Christian,
Root Katharina,
Hiss Jan A.,
Zenobi Renato,
Schneider Gisbert
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201811215
Subject(s) - peptide , a priori and a posteriori , computational biology , computer science , chemistry , peptide sequence , combinatorial chemistry , biochemistry , biology , gene , philosophy , epistemology
A computational technique based on a simulated molecular evolution protocol was employed for anticancer peptide (ACP) design. Starting from known ACPs, innovative bioactive peptides were automatically generated in computer‐assisted design–synthesize–test cycles. This design algorithm offers a viable strategy for the generation of novel peptide sequences, without requiring a priori structure–activity knowledge. Sequence morphing and activity improvement were achieved through iterative amino acid variation and selection. Results show that not only the interaction of ACPs with the target membrane is important for their anticancer activity, but also the degree of peptide dimerization, which was corroborated by temperature profiling and electrospray mass spectrometry.