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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

The biological functions of proteins often depend on dynamic structural ensembles. In this work, we develop a flow-based generative modeling approach for learning and sampling the conformational landscapes of proteins. We repurpose highly…

Biomolecules · Quantitative Biology 2024-09-04 Bowen Jing , Bonnie Berger , Tommi Jaakkola

AlphaFold predicts protein structures from the amino acid sequence at or near experimental resolution, solving the 50-year-old protein folding challenge, leading to progress by transforming large-scale genomics data into protein structures.…

Biomolecules · Quantitative Biology 2021-11-16 Bozitao Zhong , Xiaoming Su , Minhua Wen , Sichen Zuo , Liang Hong , James Lin

We have earlier reported the MOLSDOCK technique to perform rigid receptor/flexible ligand docking. The method uses the MOLS method, developed in our laboratory. In this paper we report iMOLSDOCK, the 'flexible receptor' extension we have…

Biological Physics · Physics 2017-05-08 D. Sam Paul , N. Gautham

Molecular representation learning is pivotal for various molecular property prediction tasks related to drug discovery. Robust and accurate benchmarks are essential for refining and validating current methods. Existing molecular property…

Chemical Physics · Physics 2024-06-27 Shikun Feng , Jiaxin Zheng , Yinjun Jia , Yanwen Huang , Fengfeng Zhou , Wei-Ying Ma , Yanyan Lan

After AlphaFold won the Nobel Prize, protein prediction with deep learning once again became a hot topic. We comprehensively explore advanced deep learning methods applied to protein structure prediction and design. It begins by examining…

Molecular docking is an essential tool for drug design. It helps the scientist to rapidly know if two molecules, respectively called ligand and receptor, can be combined together to obtain a stable complex. We propose a new multi-objective…

Quantitative Methods · Quantitative Biology 2008-11-05 Jean-Charles Boisson , Laetitia Jourdan , El-Ghazali Talbi , Dragos Horvath

The AlphaFold series has transformed protein structure prediction with remarkable accuracy, often matching experimental methods. AlphaFold2, AlphaFold-Multimer, and the latest AlphaFold3 represent significant strides in predicting single…

We present a computational scheme for predicting the ligands that bind to a pocket of known structure. It is based on the generation of a general abstract representation of the molecules, which is invariant to rotations, translations and…

Chemical Physics · Physics 2024-05-09 R. Beccaria , A. Lazzeri , G. Tiana

Large language models applied to vast biological datasets have the potential to transform biology by uncovering disease mechanisms and accelerating drug development. However, current models are often siloed, trained separately on…

Computational drug discovery strategies can be broadly placed in two categories: ligand-based methods which identify novel molecules by similarity with known ligands, and structure-based methods which predict molecules with high-affinity to…

Quantitative Methods · Quantitative Biology 2019-05-30 Vincent Mallet , Carlos G. Oliver , Nicolas Moitessier , Jerome Waldispuhl

We introduce IntFold, a controllable foundation model for general and specialized biomolecular structure prediction. Utilizing a high-performance custom attention kernel, IntFold achieves accuracy comparable to the state-of-the-art…

Biomolecules · Quantitative Biology 2025-07-08 The IntFold Team , Leon Qiao , Wayne Bai , He Yan , Gary Liu , Nova Xi , Xiang Zhang , Siqi Sun

Publicly available collections of drug-like molecules have grown to comprise 10s of billions of possibilities in recent history due to advances in chemical synthesis. Traditional methods for identifying "hit" molecules from a large…

Directionality in molecular and biomolecular networks plays a significant role in the accurate represention of the complex, dynamic, and asymmetrical nature of interactions present in protein-ligand binding, signal transduction, and…

Biomolecules · Quantitative Biology 2024-11-08 Mushal Zia , Benjamin Jones , Hongsong Feng , Guo-Wei Wei

Protein-ligand binding is the process by which a small molecule (drug or inhibitor) attaches to a target protein. Binding affinity, which characterizes the strength of biomolecular interactions, is essential for tackling diverse challenges…

Protein-protein docking is crucial for understanding how proteins interact. Numerous docking tools have been developed to discover possible conformations of two interacting proteins. However, the reliability and success of these docking…

Biomolecules · Quantitative Biology 2025-11-18 Azam Shirali , Vitalii Stebliankin , Jimeng Shi , Prem Chapagain , Giri Narasimhan

Predicting non-covalent host-guest recognition remains challenging due to the complex interplay of electrostatics, dispersion, and steric effects, and the limited transferability of existing docking approaches to synthetic supramolecular…

Chemical Physics · Physics 2026-01-21 Zidi Wang , Tao Zhang , Muyao Yu , Chuyi Zhou , Zezhao Xu , Huiyu Liu , Yuzhen Wen , Linjiang Chen , Jie Zheng , Shan Jiang

AlphaFold 3 represents a transformative advancement in computational biology, enhancing protein structure prediction through novel multi-scale transformer architectures, biologically informed cross-attention mechanisms, and geometry-aware…

Biomolecules · Quantitative Biology 2025-08-27 Alireza Abbaszadeh , Armita Shahlaee

In drug discovery, molecular dynamics (MD) simulation for protein-ligand binding provides a powerful tool for predicting binding affinities, estimating transport properties, and exploring pocket sites. There has been a long history of…

Accurate prediction of protein-ligand binding affinity plays a pivotal role in accelerating the discovery of novel drugs and vaccines, particularly for gastrointestinal (GI) diseases such as gastric ulcers, Crohn's disease, and ulcerative…

Machine Learning · Computer Science 2025-11-11 Ziyang Gao , Annie Cheung , Yihao Ou