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Modern AI technologies for drug discovery are distributed across heterogeneous platforms-including web applications, desktop environments, and code libraries-leading to fragmented workflows, inconsistent interfaces, and high integration…

Deep learning in \emph{de novo} protein design has achieved atomic-level fidelity. However, existing models remain largely non-deliberative: they directly synthesize molecular geometries without explicitly reasoning about which residues or…

We report a 3D structure-based method of predicting protein-protein interaction partners. It involves screening for pairs of tetrahedra representing interacting amino acids at the interface of the protein-protein complex, with one…

Biomolecules · Quantitative Biology 2015-05-06 Vicente M. Reyes

Fundamental questions about the role of the quaternary structures are addressed using a statistical mechanics off-lattice model of a dimer protein. The model, in spite of its simplicity, captures key features of the monomer-monomer…

Statistical Mechanics · Physics 2007-05-23 Cecilia Clementi , Paolo Carloni , Amos Maritan

Protein activity is a significant characteristic for recombinant proteins which can be used as biocatalysts. High activity of proteins reduces the cost of biocatalysts. A model that can predict protein activity from amino acid sequence is…

Quantitative Methods · Quantitative Biology 2018-07-23 X. Han , X. Wang , K. Zhou

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

The design of target-specific molecules such as small molecules, peptides, and antibodies is vital for biological research and drug discovery. Existing generative methods are restricted to single-domain molecules, failing to address…

Machine Learning · Computer Science 2025-05-27 Xiangzhe Kong , Zishen Zhang , Ziting Zhang , Rui Jiao , Jianzhu Ma , Wenbing Huang , Kai Liu , Yang Liu

Protein-ligand structure prediction is an essential task in drug discovery, predicting the binding interactions between small molecules (ligands) and target proteins (receptors). Recent advances have incorporated deep learning techniques to…

This paper demonstrates that language models are strong structure-based protein designers. We present LM-Design, a generic approach to reprogramming sequence-based protein language models (pLMs), that have learned massive sequential…

Machine Learning · Computer Science 2023-02-10 Zaixiang Zheng , Yifan Deng , Dongyu Xue , Yi Zhou , Fei YE , Quanquan Gu

The cornerstone of computational drug design is the calculation of binding affinity between two biological counterparts, especially a chemical compound, i.e., a ligand, and a protein. Predicting the strength of protein-ligand binding with…

Biomolecules · Quantitative Biology 2019-12-04 Yanjun Li , Mohammad A. Rezaei , Chenglong Li , Xiaolin Li , Dapeng Wu

Generative machine learning models are increasingly being used to design novel proteins for therapeutic and biotechnological applications. However, the current methods mostly focus on the design of proteins with a fixed backbone structure,…

Biomolecules · Quantitative Biology 2025-03-04 Petr Kouba , Joan Planas-Iglesias , Jiri Damborsky , Jiri Sedlar , Stanislav Mazurenko , Josef Sivic

Protein language models have shown remarkable success in learning biological information from protein sequences. However, most existing models are limited by either autoencoding or autoregressive pre-training objectives, which makes them…

Quantitative Methods · Quantitative Biology 2024-12-10 Bo Chen , Xingyi Cheng , Pan Li , Yangli-ao Geng , Jing Gong , Shen Li , Zhilei Bei , Xu Tan , Boyan Wang , Xin Zeng , Chiming Liu , Aohan Zeng , Yuxiao Dong , Jie Tang , Le Song

The accurate screening of candidate drug ligands against target proteins through computational approaches is of prime interest to drug development efforts. Such virtual screening depends in part on methods to predict the binding affinity…

Machine Learning · Computer Science 2024-10-22 Ho-Joon Lee , Prashant S. Emani , Mark B. Gerstein

Nucleic acid-based drugs like aptamers have recently demonstrated great therapeutic potential. However, experimental platforms for aptamer screening are costly, and the scarcity of labeled data presents a challenge for supervised methods to…

Biomolecules · Quantitative Biology 2024-11-05 Tinglin Huang , Zhenqiao Song , Rex Ying , Wengong Jin

Antibodies are versatile proteins that can bind to pathogens and provide effective protection for human body. Recently, deep learning-based computational antibody design has attracted popular attention since it automatically mines the…

Biomolecules · Quantitative Biology 2022-11-18 Kaiyuan Gao , Lijun Wu , Jinhua Zhu , Tianbo Peng , Yingce Xia , Liang He , Shufang Xie , Tao Qin , Haiguang Liu , Kun He , Tie-Yan Liu

Predicting the effect of mutations in proteins is one of the most critical challenges in protein engineering; by knowing the effect a substitution of one (or several) residues in the protein's sequence has on its overall properties, could…

Computational Engineering, Finance, and Science · Computer Science 2020-10-08 David Medina-Ortiz , Sebastian Contreras , Juan Amado-Hinojosa , Jorge Torres-Almonacid , Juan A. Asenjo , Marcelo Navarrete , Álvaro Olivera-Nappa

Deep learning is catalyzing a scientific revolution fueled by big data, accessible toolkits, and powerful computational resources, impacting many fields including protein structural modeling. Protein structural modeling, such as predicting…

Biomolecules · Quantitative Biology 2020-07-17 Wenhao Gao , Sai Pooja Mahajan , Jeremias Sulam , Jeffrey J. Gray

Structure-based drug design (SBDD) aims to discover drug candidates by finding molecules (ligands) that bind tightly to a disease-related protein (targets), which is the primary approach to computer-aided drug discovery. Recently, applying…

Quantitative Methods · Quantitative Biology 2022-12-01 Tianfan Fu , Wenhao Gao , Connor W. Coley , Jimeng Sun

We introduce AMix-1, a powerful protein foundation model built on Bayesian Flow Networks and empowered by a systematic training methodology, encompassing pretraining scaling laws, emergent capability analysis, in-context learning mechanism,…

Figuring out small molecule binding sites in target proteins, in the resolution of either pocket or residue, is critical in many virtual and real drug-discovery scenarios. Since it is not always easy to find such binding sites based on…

Quantitative Methods · Quantitative Biology 2023-04-19 Daeseok Lee , Jeunghyun Byun , Bonggun Shin