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Updated: Jun 12, 2026

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
New compstatin variants through two de novo protein design frameworks
M L Bellows1, H K Fung, M S Taylor
1Department of Chemical Engineering, Princeton University, Princeton, New Jersey, USA.
Abstract:
Two de novo protein design frameworks are applied to the discovery of new compstatin variants. One is based on sequence selection and fold specificity, whereas the other approach is based on sequence selection and approximate binding affinity calculations. The proposed frameworks were applied to a complex of C3c with compstatin variant E1 and new variants with improved binding affinities are predicted and experimentally validated. The computational studies elucidated key positions in the sequence of compstatin that greatly affect the binding affinity. Positions 4 and 13 were found to favor Trp, whereas positions 1, 9, and 10 are dominated by Asn, and position 11 consists mainly of Gln. A structural analysis of the C3c-bound peptide analogs is presented.
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