A multiobjective evolutionary method for the design of peptidic mimotopes.
Peptides that mimic protein epitopes are interesting drug candidates. However, the design of effective peptidic drugs is difficult for several reasons, such as the fast degradation of peptides, their high flexibility, and thus high entropy loss on binding to the target. We therefore propose an in silico method for the automated design of peptides that are optimal with respect to several objectives. We present a Pareto-based multiobjective evolutionary algorithm for in silico peptide design. Using a simple molecular model, we apply the method to the design of peptides that (a) mimic antibody epitopes of the proteins thrombin and blood coagulation factor VIII, respectively, that (b) are short, and (c) are conformationally stable.
Research Group Functional Peptides, Ludwig-Erhard-Allee 2, D-53175 Bonn, Germany. Tim.Hohm@caesar.de
Tim
T
Hohm
Philipp
P
Limbourg
Daniel
D
Hoffmann
D000465:Algorithms; D019295:Computational Biology; D019020:Directed Molecular Evolution / Q000379:methods*; D000939:Epitopes / Q000737:chemistry / Q000235:genetics*; D005169:Factor VIII / Q000138:chemical synthesis / Q000235:genetics; D006801:Humans; D009154:Mutation; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000235:genetics*; D017510:Protein Folding; D013917:Thrombin / Q000138:chemical synthesis / Q000235:genetics
D000939:Epitopes; D010446:Peptide Fragments; D005169:Factor VIII; D013917:Thrombin