2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
September 2nd, 2025
Version: 2
ByteDance
molecular biology
bioRxiv

PXDesign: Fast, Modular, and Accurate De Novo Design of Protein Binders

Ren, M.Open in Google Scholar•Sun, J.Open in Google Scholar•Guan, J.Open in Google Scholar•Liu, C.Open in Google Scholar•Gong, C.Open in Google Scholar•Wang, Y.Open in Google Scholar•Wang, L.Open in Google Scholar•Cai, Q.Open in Google Scholar•Chen, X.Open in Google Scholar•Xiao, W.Open in Google Scholar

PXDesign achieves nanomolar binder hit rates of 20-73% across five of six diverse protein targets, surpassing prior methods such as AlphaProteo. This experimental success rate is enabled by advances in both binder generation and filtering. We develop both a diffusion-based generative model (PXDesign-d) and a hallucination-based approach (PXDesign-h), each showing strong in silico performance that outperforms existing models. Beyond generation, we systematically analyze confidence-based filtering and ranking strategies from multiple structure predictors, comparing their accuracy, efficiency, and complementarity on datasets spanning de novo binders and mutagenesis. Finally, we validate the full design process experimentally, achieving high hit rates and multiple nanomolar binders. To support future work and community use, we release a unified benchmarking framework at https://github.com/bytedance/PXDesignBench, provide public access to PXDesign via a webserver at https://protenix-server.com, and share all designed binder sequences at https: //protenix.github.io/pxdesign.

Similar Papers

bioRxiv
Tue Sep 02 2025
Mapping early PRC2 nucleation sites upon Suz12 reintroduction reveals features of de novo Polycomb recruitment
Polycomb domains safeguard cell identity by maintaining lineage-specific chromatin states enriched in repressive histone modifications, preserving the epigenetic memory of cell lineages. While Polycomb Repressive Complex 2 (PRC2) can re-establish its occupancy after perturbation, the mechanisms that guide de novo Polycomb recruitment remain unclear. To address this, we engineered an auxin-inducibl...
Hernandez-Romero, I. A.
•
Peralta-Alvarez, C. A.
•
Roman-Figueroa, A.
•
Cano-Dominguez, N.
...•
Valdes, J.
bioRxiv
Mon Sep 01 2025
Cellular dynamics and epidermal specialization during Arabidopsis floral development at single-cell resolution
Cellular specialization underlies the functional diversification of floral organs, yet the regulatory networks driving epidermal differentiation remain poorly understood. Here, we constructed a single-nucleus transcriptomic atlas of developing Arabidopsis thaliana flowers by profiling over 70,000 nuclei. For annotation of single-cell identities and differentiation status, we additionally generated...
Chen, S.
•
Neumann, M.
•
He, Z.
•
Carew, F.
...•
Kaufmann, K.
bioRxiv
Mon Sep 01 2025
HPF1 REGULATES THE FORMATION OF FUS-DEPENDENT COMPARTMENTS BY PARP1 AND PARP2 ACTIVATION ON DAMAGED DNA
FUS participates in the formation of biomolecular condensates associated with PARP1-dependent synthesis of poly(ADP-ribose) (PAR). HPF1 regulates auto- and hetero-PARylation activities of PARP1 and PARP2 and may influence the formation of FUS compartments during PARP1 or PARP2 auto-PARylation. In this study, we used atomic force microscopy in combination with biochemical assay to investigate the f...
Singatulina, A. S.
•
Sukhanova, M. V.
•
Hamon, L.
•
Kutuzov, M. M.
...•
Lavrik, O.
bioRxiv
Mon Sep 01 2025
Locations of consecutive G·C base-pairs direct genomic nucleosome positioning
The nucleosome is a structural and functional subunit of chromatin, and its positioning and dynamics in the eukaryotic genomes serves as a key platform for gene regulation. Here, we determine the positions of fully wrapped nucleosomes across the yeast genome by chemical mapping through the histone H2A-A122C residue, which cleaves near the DNA entry/exit sites. This approach reveals the most refine...
Kato, H.
•
Fuse, T.
•
Sato, S.
•
Kurihara, Y.
...•
Shimizu, M.
bioRxiv
Mon Sep 01 2025
Reliable Detection of SGLT2 Protein through Knockout-based Antibody Characterization and Optimized Procedures
Introduction: Sodium-glucose cotransporter 2 (SGLT2) is a key mediator of renal glucose reabsorption. Its pharmacological inhibition exerts cardiac- and reno-protective benefits. Despite widespread clinical interest, reliable detection of SGLT2 protein remains challenging due to concerns regarding the specificity of available antibodies. Methods: This study assessed the specificity of eight commer...
Hirose, T.
•
Ito, H.
•
Endo, A.
•
Sato, S.
...•
Mori, T.
bioRxiv
Mon Sep 01 2025
Mycoplasma gallisepticum FtsZ demonstrates properties that distinguish it from other known homologs
In bacteria, cell division usually occurs through binary fission, with the participation of genes from the dcw cluster. In mollicutes, this cluster is significantly reduced - often only the ftsZ, ftsA, mraZ, and mraW genes remain, and sometimes ftsZ is completely absent. FtsZ is a key division protein that forms the Z-ring, but its role in mollicutes is questionable due to the absence of many cell...
Rumyantseva, N. A.
•
Golofeeva, D. M.
•
Khasanova, A. A.
•
Shabalina, A. V.
...•
Vedyaykin, A.
bioRxiv
Mon Sep 01 2025
MeCP2 binding and genome-lamina reorganization precede long gene activation during mouse corticogenesis
During corticogenesis, neural gene expression is tightly coordinated by chromatin and epigenetic changes, whose misregulation can lead to neurodevelopmental disorders. The role of spatial genome organization - particularly interactions with the nuclear lamina - during these developmental programs remains poorly understood. Here, we combined in utero electroporation with scDam&T-seq to jointly prof...
Rullens, P. M. J.
•
de Vries, S. S.
•
Lochs, S. J. A.
•
Markodimitraki, C. M.
...•
Kind, j.
bioRxiv
Mon Sep 01 2025
Poly(UG)-tailed RNAs are involved in the control of thousands of genes predominantly in the germline in Pristionchus pacificus
In the nematode Caenorhabditis elegans, the terminal transferase RDE-3 adds a poly(UG)-tail to the free 3\' end of RNA molecules generated by the action of primary siRNAs or piRNAs. The tailed RNA serves as a template for RNA-dependent RNA polymerases (RdRp) to generate secondary siRNAs, thereby reinforcing the RNAi effect. In this iterative process, progressively shorter tailed RNAs are formed. I...
de Ree, V.
•
Harbecke, D.
•
Witte, H.
•
Roedelsperger, C.
...•
Streit, A.
bioRxiv
Mon Sep 01 2025
PDS5 proteins control genome architecture by limiting the lifetime of cohesin-NIPBL complexes
Cohesin-NIPBL complexes extrude genomic DNA into loops that are constrained by CTCF boundaries. This process has important regulatory functions and weakens the separation between euchromatic and heterochromatic compartments. Cohesin can also bind PDS5A or PDS5B, which do not support loop extrusion but are required for the formation of CTCF boundaries. How PDS5 proteins perform this function is unk...
Wutz, G.
•
Davidson, I. F.
•
Banigan, E. J.
•
Kawasumi, R.
...•
Peters, J. M.