Protein Design by Optimization of a Sequence-Structure Quality Function

Anautomatedprocedurefor protein designbyoptimization of a sequence-structurequalityhasbeendeveloped. Themethodselectsa statistically optimalsequencefor a particularstructure,ontheassumptionthat sucha protein will adoptthe desiredstructure. Wepresenttwooptimization algorithms:oneprovidesan exact optimization whilethe otherusesa combinatorialtechniquefor comparativelyrapidresults. Bothare suitablefor massively parallel computers.Aprototype systemwasused to design sequenceswhichshouldadopt the four-helix bundleconformationof myohemerythrin.Theseappear satisfactoryto secondarystructureandprofileanalysis. Detailedinspectionrevealsthat the sequencesare generally plausiblebut, as expected,lacksomespecificstructural features. Thedesign parametersprovidesome insightintothe generaldeterminantsof proteinstructure.

• Type: Conference
• Year: 1994
• Where: ISMB
• Authors: Steven E. Brenner, Alan Berry
• Keywords: Computational Biology, ISMB 1994, Ontheassumptionthat Sucha Protein, Particularstructure, Protein Designbyoptimization