PartiDesign: A structure-sequence co-design paradigm for practical all-to-all biomolecules design
- 1School of Pharmacy, Zhejiang University, Hangzhou 310058, China
Abstract
Engineering interactions among biomolecules offers a route to creating new biological functions. Although unified models have advanced biomolecular structure prediction and design, efficient and controllable generation across molecular modalities remains challenging. A key challenge is to couple three-dimensional structure generation with sequence or chemical-identity design across chemically diverse systems. Here, we introduce PartiDesign, a unified structure-sequence co-design model that extends the partially latent framework of La-Proteina to proteins, nucleic acids and small molecules. PartiDesign jointly generates molecular structures and their corresponding sequences or chemical identities, while providing fine-grained control over secondary structure, chemical bonding and amino acid preferences. Across diverse benchmarks for the de novo design of proteins, nucleic acids and small molecules against specified targets, PartiDesign achieved the highest estimated successful-design throughput among the evaluated methods on most benchmarks under the adopted compute-budget protocols. Its configurable constraints further support cyclic peptide and antibody design, allowing generation to be tailored to specific structural and chemical requirements. PartiDesign was developed using 128 Huawei Ascend 910B accelerators, each with 64 GB of memory. The source code is available at https://github.com/MegaGatlingPea/PartiDesign-official, and a freely accessible web server at https://cadd.zju.edu.cn/partidesign/ enables users to generate binding partners without programming expertise. Together, these capabilities provide a versatile and accessible framework for all-to-all biomolecular design, with applications in molecular engineering and drug discovery.
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BibTeX
@misc{jin2026partidesign,
title = {{PartiDesign: A structure-sequence co-design paradigm for practical all-to-all biomolecules design}},
author = {Z. Jin and X. Zhang and Y. Kang and T. Hou},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.03.763860},
url = {https://www.biorxiv.org/content/10.64898/2026.11.03.763860v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - PartiDesign: A structure-sequence co-design paradigm for practical all-to-all biomolecules design
AU - Z. Jin
AU - X. Zhang
AU - Y. Kang
AU - T. Hou
PY - 2026
DA - 2026/11/03
PB - bioRxiv
DO - 10.64898/2026.11.03.763860
UR - https://www.biorxiv.org/content/10.64898/2026.11.03.763860v1
AB - Engineering interactions among biomolecules offers a route to creating new biological functions. Although unified models have advanced biomolecular structure prediction and design, efficient and controllable generation across molecular modalities remains challenging. A key challenge is to couple three-dimensional structure generation with sequence or chemical-identity design across chemically diverse systems. Here, we introduce PartiDesign, a unified structure-sequence co-design model that extends the partially latent framework of La-Proteina to proteins, nucleic acids and small molecules. PartiDesign jointly generates molecular structures and their corresponding sequences or chemical identities, while providing fine-grained control over secondary structure, chemical bonding and amino acid preferences. Across diverse benchmarks for the de novo design of proteins, nucleic acids and small molecules against specified targets, PartiDesign achieved the highest estimated successful-design throughput among the evaluated methods on most benchmarks under the adopted compute-budget protocols. Its configurable constraints further support cyclic peptide and antibody design, allowing generation to be tailored to specific structural and chemical requirements. PartiDesign was developed using 128 Huawei Ascend 910B accelerators, each with 64 GB of memory. The source code is available at https://github.com/MegaGatlingPea/PartiDesign-official, and a freely accessible web server at https://cadd.zju.edu.cn/partidesign/ enables users to generate binding partners without programming expertise. Together, these capabilities provide a versatile and accessible framework for all-to-all biomolecular design, with applications in molecular engineering and drug discovery.
ER -