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The binding complexes formed by proteins and small molecule ligands are ubiquitous and critical to life. Despite recent advancements in protein structure prediction, existing algorithms are so far unable to systematically predict the…

Quantitative Methods · Quantitative Biology 2023-04-21 Zhuoran Qiao , Weili Nie , Arash Vahdat , Thomas F. Miller , Anima Anandkumar

Proteins play a critical role in carrying out biological functions, and their 3D structures are essential in determining their functions. Accurately predicting the conformation of protein side-chains given their backbones is important for…

Quantitative Methods · Quantitative Biology 2024-02-19 Yangtian Zhang , Zuobai Zhang , Bozitao Zhong , Sanchit Misra , Jian Tang

Even with the significant advances of AlphaFold-Multimer (AF-Multimer) and AlphaFold3 (AF3) in protein complex structure prediction, their accuracy is still not comparable with monomer structure prediction. Efficient quality assessment (QA)…

Biomolecules · Quantitative Biology 2024-10-24 Bingqing Han , Yipeng Zhang , Longlong Li , Xinqi Gong , Kelin Xia

Protein-protein interactions (PPIs) are governed by surface complementarity and hydrophobic interactions at protein interfaces. However, designing diverse and physically realistic protein structure and surfaces that precisely complement…

Machine Learning · Computer Science 2025-11-24 Guanlue Li , Xufeng Zhao , Fang Wu , Sören Laue

Consistency and reliability are crucial for conducting AI research. Many famous research fields, such as object detection, have been compared and validated with solid benchmark frameworks. After AlphaFold2, the protein folding task has…

Biomolecules · Quantitative Biology 2023-08-01 Jaemyung Lee , Kyeongtak Han , Jaehoon Kim , Hasun Yu , Youhan Lee

We present TerraBind, a foundation model for protein-ligand structure and binding affinity prediction that achieves 26-fold faster inference than state-of-the-art methods while improving affinity prediction accuracy by $\sim$20\%. Current…

Inverse protein folding generates valid amino acid sequences that can fold into a desired protein structure, with recent deep-learning advances showing strong potential and competitive performance. However, challenges remain, such as…

Biomolecules · Quantitative Biology 2025-07-29 Peizhen Bai , Filip Miljković , Xianyuan Liu , Leonardo De Maria , Rebecca Croasdale-Wood , Owen Rackham , Haiping Lu

Deep learning approaches have produced substantial breakthroughs in fields such as image classification and natural language processing and are making rapid inroads in the area of protein design. Many generative models of proteins have been…

Machine Learning · Computer Science 2021-09-29 Alexey Strokach , Philip M. Kim

AlphaFold 3 (AF3), the latest version of protein structure prediction software, goes beyond its predecessors by predicting protein-protein complexes. It could revolutionize drug discovery and protein engineering, marking a major step…

Biomolecules · Quantitative Biology 2024-06-07 JunJie Wee , Guo-Wei Wei

Diffusion generative models have emerged as a powerful framework for addressing problems in structural biology and structure-based drug design. These models operate directly on 3D molecular structures. Due to the unfavorable scaling of…

Biomolecules · Quantitative Biology 2024-05-10 Ian Dunn , David Ryan Koes

Predicting the impact of single-point amino acid mutations on protein stability is essential for understanding disease mechanisms and advancing drug development. Protein stability, quantified by changes in Gibbs free energy ($\Delta\Delta…

Machine Learning · Computer Science 2025-01-31 Karishma Thakrar , Jiangqin Ma , Max Diamond , Akash Patel

Deep Learning (DL) algorithms hold great promise for applications in the field of computational biophysics. In fact, the vast amount of available molecular structures, as well as their notable complexity, constitutes an ideal context in…

Soft Condensed Matter · Physics 2019-01-07 Marco Giulini , Raffaello Potestio

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

In silico prediction of the ligand binding pose to a given protein target is a crucial but challenging task in drug discovery. This work focuses on blind flexible selfdocking, where we aim to predict the positions, orientations and…

Biomolecules · Quantitative Biology 2023-06-02 Yangtian Zhang , Huiyu Cai , Chence Shi , Bozitao Zhong , Jian Tang

Systematic identification of protein function is a key problem in current biology. Most traditional methods fail to identify functionally equivalent proteins if they lack similar sequences, structural data or extensive manual annotations.…

Genomics · Quantitative Biology 2016-03-08 Dan Ofer

The design of novel proteins has many applications but remains an attritional process with success in isolated cases. Meanwhile, deep learning technologies have exploded in popularity in recent years and are increasingly applicable to…

Biomolecules · Quantitative Biology 2018-11-07 Joe G Greener , Lewis Moffat , David T Jones

This paper investigates the application of the transformer architecture in protein folding, as exemplified by DeepMind's AlphaFold project, and its implications for the understanding of so-called large language models. The prevailing…

Computers and Society · Computer Science 2024-12-10 Fabian Offert , Paul Kim , Qiaoyu Cai

Protein representation learning is critical in various tasks in biology, such as drug design and protein structure or function prediction, which has primarily benefited from protein language models and graph neural networks. These models…

Biomolecules · Quantitative Biology 2024-02-16 Bozhen Hu , Zelin Zang , Cheng Tan , Stan Z. Li

Computational elucidation of membrane protein (MP) structures is challenging partially due to lack of sufficient solved structures for homology modeling. Here we describe a high-throughput deep transfer learning method that first predicts…

Biomolecules · Quantitative Biology 2017-08-29 Sheng Wang , Zhen Li , Yizhou Yu , Jinbo Xu

We introduce RosettaSearch, an inference-time multi-objective optimization approach for backbone conditioned protein sequence design. We use large language models (LLMs) as a generative optimizer within a search algorithm capable of…

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