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Deep learning has transformed protein design, enabling accurate structure prediction, sequence optimization, and de novo protein generation. Advances in single-chain protein structure prediction via AlphaFold2, RoseTTAFold, ESMFold, and…

Machine Learning · Computer Science 2025-02-27 Gregory W. Kyro , Tianyin Qiu , Victor S. Batista

Artificial intelligence (AI) in the form of deep learning bears promise for drug discovery and chemical biology, $\textit{e.g.}$, to predict protein structure and molecular bioactivity, plan organic synthesis, and design molecules…

Biomolecules · Quantitative Biology 2022-12-29 Rıza Özçelik , Derek van Tilborg , José Jiménez-Luna , Francesca Grisoni

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…

The quest for accurate prediction of drug molecule properties poses a fundamental challenge in the realm of Artificial Intelligence Drug Discovery (AIDD). An effective representation of drug molecules emerges as a pivotal component in this…

Machine Learning · Computer Science 2024-04-22 Zhuoyuan Wang , Jiacong Mi , Shan Lu , Jieyue He

Molecular core structures and R-groups are essential concepts in drug development. Integration of these concepts with conventional graph pre-training approaches can promote deeper understanding in molecules. We propose MolPLA, a novel…

Machine Learning · Computer Science 2024-01-31 Mogan Gim , Jueon Park , Soyon Park , Sanghoon Lee , Seungheun Baek , Junhyun Lee , Ngoc-Quang Nguyen , Jaewoo Kang

Structure-based drug design (SBDD) leverages the 3D structure of biomolecular targets to guide the creation of new therapeutic agents. Recent advances in generative models, including diffusion models and geometric deep learning, have…

Biomolecules · Quantitative Biology 2025-01-28 Ali Khodabandeh Yalabadi , Mehdi Yazdani-Jahromi , Ozlem Ozmen Garibay

Molecules are graphs, but large language models~(LLMs) are usually asked to reason about them through linear strings. The most popular molecular representation, SMILES, compresses atoms, bonds, branches and rings into a compact sequence in…

Biomolecules · Quantitative Biology 2026-05-19 Zhiyuan Yan , Chen Liu , Boxuan Zhao , Kaiqing Lin , Jixiang Zhao , Yimi Wang , Liuzhenghao Lv , Hao Li , Shanzhuo Zhang , Li Yuan , Fanyang Mo

A variety of methods have been proposed for structure similarity calculation, which are called structure alignment or superposition. One major shortcoming in current structure alignment algorithms is in their inherent design, which is based…

Quantitative Methods · Quantitative Biology 2013-07-31 Xuefeng Cui , Shuai Cheng Li , Dongbo Bu , Ming Li

Diffusion models have achieved promising results for Structure-Based Drug Design (SBDD). Nevertheless, high-quality protein subpocket and ligand data are relatively scarce, which hinders the models' generation capabilities. Recently, Direct…

Biomolecules · Quantitative Biology 2026-02-11 Xiwei Cheng , Xiangxin Zhou , Yuwei Yang , Yu Bao , Quanquan Gu

PyMOLfold is a flexible and open-source plugin designed to seamlessly integrate AI-based protein structure prediction and visualization within the widely used PyMOL molecular graphics system. By leveraging state-of-the-art protein folding…

Biomolecules · Quantitative Biology 2025-02-04 Colby T. Ford , Samee Ullah , Dinler Amaral Antunes , Tarsis Gesteira Ferreira

Designing compounds with desired properties is a key element of the drug discovery process. However, measuring progress in the field has been challenging due to the lack of realistic retrospective benchmarks, and the large cost of…

Biomolecules · Quantitative Biology 2023-06-16 Tobiasz Cieplinski , Tomasz Danel , Sabina Podlewska , Stanislaw Jastrzebski

Designing protein sequences that fold into a target 3-D structure, termed as the inverse folding problem, is central to protein engineering. However, it remains challenging due to the vast sequence space and the importance of local…

Quantitative Methods · Quantitative Biology 2026-03-17 Sazan Mahbub , Souvik Kundu , Eric P. Xing

Designing proteins with desired functions or properties represents a core goal in synthetic biology and drug discovery. Recent advances in protein language models (PLMs) have enabled the generation of highly designable protein sequences,…

Machine Learning · Computer Science 2026-05-12 Yulin Zhang , He Cao , Zihao Jiang , Chenyi Zi , Zhipeng Zhou , Zijing Liu , Yu Li , Jia Li , Ziqi Gao

Every molecule ever synthesised can be drawn as a 2D skeletal diagram, yet in modern property prediction this universally available representation has received less focus in favour of molecular graphs, 3D conformers, or billion-parameter…

Computer Vision and Pattern Recognition · Computer Science 2026-05-12 Aaditya Baranwal , Akshaj Gupta , Shruti Vyas , Yogesh S Rawat

Proteins perform their biological functions through three-dimensional structures encoded by amino acid sequences, and ligand-binding protein co-design requires models that generate sequence-structure compatible proteins under explicit…

Biomolecules · Quantitative Biology 2026-05-28 Chen Wei , Fanding Xu , Minghao Sun , Zhiyuan Liu , Lin Wang , Tianrui Jia , Yihang Zhou , Yang Zhang

Recent remarkable advancements in geometric deep generative models, coupled with accumulated structural data, enable structure-based drug design (SBDD) using only target protein information. However, existing models often struggle to…

Biomolecules · Quantitative Biology 2026-03-09 Joongwon Lee , Wonho Zhung , Jisu Seo , Woo Youn Kim

Proteins adopt multiple structural conformations to perform their diverse biological functions, and understanding these conformations is crucial for advancing drug discovery. Traditional physics-based simulation methods often struggle with…

Biomolecules · Quantitative Biology 2025-03-14 Jiarui Lu , Xiaoyin Chen , Stephen Zhewen Lu , Chence Shi , Hongyu Guo , Yoshua Bengio , Jian Tang

Proteins are the major building blocks of life, and actuators of almost all chemical and biophysical events in living organisms. Their native structures in turn enable their biological functions which have a fundamental role in drug design.…

Accurately assigning folds for divergent protein sequences is a major obstacle to structural studies and underlies the inverse protein folding problem. Herein, we outline our theories for fold-recognition in the "twilight-zone" of sequence…

Quantitative Methods · Quantitative Biology 2010-08-31 Yoojin Hong , Kyung Dae Ko , Gaurav Bhardwaj , Zhenhai Zhang , Damian B. van Rossum , Randen L. Patterson

Deep learning has become a crucial tool in studying proteins. While the significance of modeling protein structure has been discussed extensively in the literature, amino acid types are typically included in the input as a default operation…

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