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Intrinsically disordered regions (IDRs) account for one-third of the human proteome and play essential biological roles. However, predicting the functions of IDRs remains a major challenge due to their lack of stable structures, rapid…

Biomolecules · Quantitative Biology 2025-07-04 Đesika Kolarić , Chi Fung Willis Chow , Rita Zi Zhu , Agnes Toth-Petroczy , T. Reid Alderson , Iva Pritišanac

Although machine learning has transformed protein structure prediction of folded protein ground states with remarkable accuracy, intrinsically disordered proteins and regions (IDPs/IDRs) are defined by diverse and dynamical structural…

Biomolecules · Quantitative Biology 2025-04-01 Oufan Zhang , Zi Hao Liu , Julie D Forman-Kay , Teresa Head-Gordon

Intrinsically disordered proteins (IDPs) constitute a broad set of proteins with few uniting and many diverging properties. IDPs-and intrinsically disordered regions (IDRs) interspersed between folded domains-are generally characterized as…

Biomolecules · Quantitative Biology 2021-06-03 Kresten Lindorff-Larsen , Birthe B. Kragelund

Recent advances in de novo protein binder design have enabled increasing experimental validation, yet reported in silico metrics remain difficult to interpret or compare across studies due to non-standardized evaluation protocols. We…

Quantitative Methods · Quantitative Biology 2026-05-25 Cong Liu , Milong Ren , Jiaqi Guan , Chengyue Gong , Jinyuan Sun , Xinshi Chen , Wenzhi Xiao

Recent years have witnessed a surge in the development of protein foundation models, significantly improving performance in protein prediction and generative tasks ranging from 3D structure prediction and protein design to conformational…

Quantitative Methods · Quantitative Biology 2024-10-08 Fei Ye , Zaixiang Zheng , Dongyu Xue , Yuning Shen , Lihao Wang , Yiming Ma , Yan Wang , Xinyou Wang , Xiangxin Zhou , Quanquan Gu

In 1999 Wright and Dyson highlighted the fact that large sections of the proteome of all organisms are comprised of protein sequences that lack globular folded structures under physiological conditions. Since then the biophysics community…

Biological Physics · Physics 2024-09-05 Zi Hao Liu , Maria Tsanai , Oufan Zhang , Julie Forman-Kay , Teresa Head-Gordon

Disordered proteins play essential roles in myriad cellular processes, yet their structural characterization remains a major challenge due to their dynamic and heterogeneous nature. We here present a community-driven initiative to address…

The prediction of intrinsic disorder regions has significant implications for understanding protein functions and dynamics. It can help to discover novel protein-protein interactions essential for designing new drugs and enzymes. Recently,…

Machine Learning · Computer Science 2025-08-19 Krzysztof Kotowski , Irena Roterman , Katarzyna Stapor

Protein design has the potential to revolutionize biotechnology and medicine. While most efforts have focused on proteins with well-defined structures, increased recognition of the functional significance of intrinsically disordered…

Biomolecules · Quantitative Biology 2025-09-17 Giulio Tesei , Francesco Pesce , Kresten Lindorff-Larsen

Intrinsically disordered proteins and regions are increasingly appreciated for their abundance in the proteome and the many functional roles they play in the cell. In this short review, we describe a variety of approaches used to obtain…

Biological Physics · Physics 2024-12-31 Zi Hao Liu , Maria Tsanai , Oufan Zhang , Teresa Head-Gordon , Julie Forman-Kay

Protein structure prediction has advanced significantly with the introduction of AlphaFold3, a diffusion-based model capable of predicting complex biomolecular interactions across proteins, nucleic acids, small molecules, and ions. While…

Quantitative Methods · Quantitative Biology 2025-11-12 Shreya Gopalan , Sundar Narayanan

The DisProt database is a significant resource containing manually curated data on experimentally validated intrinsically disordered proteins (IDPs) and regions (IDRs) from the literature. Developed in 2005, its primary goal was to collect…

Intrinsically disordered regions (IDRs) of proteins mediate sequence-specific interactions underlying diverse cellular processes, including the formation of biomolecular condensates. Although IDRs strongly influence condensate compositions,…

Soft Condensed Matter · Physics 2026-03-10 Zhuang Liu , Beijia Yuan , Mihir Rao , Gautam Reddy , William M. Jacobs

In contrast to their remarkable performance on general knowledge QA, the true abilities of Large Language Models (LLMs) in tasks demanding deep, specialized reasoning, such as in protein biology, have yet to be thoroughly investigated.…

Quantitative Methods · Quantitative Biology 2025-12-30 Dingyi Rong , Zijian Chen , Qi Jia , Kaiwei Zhang , Haotian Lu , Guangtao Zhai , Ning Liu

Proteins perform critical processes in all living systems: converting solar energy into chemical energy, replicating DNA, as the basis of highly performant materials, sensing and much more. While an incredible range of functionality has…

Biomolecules · Quantitative Biology 2021-09-29 Leonardo V. Castorina , Rokas Petrenas , Kartic Subr , Christopher W. Wood

Structure-based protein design has attracted increasing interest, with numerous methods being introduced in recent years. However, a universally accepted method for evaluation has not been established, since the wet-lab validation can be…

Quantitative Methods · Quantitative Biology 2023-12-04 Chuanrui Wang , Bozitao Zhong , Zuobai Zhang , Narendra Chaudhary , Sanchit Misra , Jian Tang

Predicting protein complex structures is essential for protein function analysis, protein design, and drug discovery. While AI methods like AlphaFold can predict accurate structural models for many protein complexes, reliably estimating the…

Biomolecules · Quantitative Biology 2025-05-30 Pawan Neupane , Jian Liu , Jianlin Cheng

Tandem mass spectrometry provides a high-throughput framework for identifying and quantifying proteins in complex biological samples. In computational proteomics, predicting peptide MS/MS spectra is a critical task, enabling downstream…

Machine Learning · Computer Science 2026-05-05 Zhiwen Yang , Pan Liu , Yifan Li , Yunhua Zhong , Jun Xia

Intrinsically Disordered Proteins (IDPs) constitute a large and structure-less class of proteins with significant functions. The existence of IDPs challenges the conventional notion that the biological functions of proteins rely on their…

Biomolecules · Quantitative Biology 2024-11-26 Parisa Mollaei , Danush Sadasivam , Chakradhar Guntuboina , Amir Barati Farimani

Understanding protein solubility is essential for their functional applications. Computational methods for predicting protein solubility are crucial for reducing experimental costs and enhancing the efficiency and success rates of protein…

Quantitative Methods · Quantitative Biology 2024-07-01 Yang Tan , Jia Zheng , Liang Hong , Bingxin Zhou
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