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Multi-objective optimization for designing structurally similar proteins with diverse sequences

Akiba, R.; Moriwaki, Y.; Ishitani, R.; Yoshikawa, N.

2025-09-17 bioinformatics
10.1101/2025.09.13.676063 bioRxiv
Show abstract

Recent advances in artificial intelligence technologies have accelerated the development of computational protein design techniques. Although the structure of the designed proteins has been the primary focus, diversity of designed amino acid sequences is another important aspect of protein design. To address the trade-off between reducing sequence similarity and improving structural similarity, simultaneous optimization of these two objectives can be effective. We present a method that integrates ProteinMPNN with the multi-objective optimization algorithm NSGA-II to design proteins that retain high structural similarity to a target while exhibiting low sequence similarity. Using Top7 as a reference protein, we demonstrate that our approach improves sequence diversity compared to the original ProteinMPNN while maintaining comparable structural similarity.

Published in Science and Technology of Advanced Materials: Methods · not in our set (fewer than 10 published preprints to learn from) · training set

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