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This work introduces GeoDirDock (GDD), a novel approach to molecular docking that enhances the accuracy and physical plausibility of ligand docking predictions. GDD guides the denoising process of a diffusion model along geodesic paths…

Biomolecules · Quantitative Biology 2024-04-10 Raúl Miñán , Javier Gallardo , Álvaro Ciudad , Alexis Molina

Structure based ligand discovery is one of the most successful approaches for augmenting the drug discovery process. Currently, there is a notable shift towards machine learning (ML) methodologies to aid such procedures. Deep learning has…

Machine Learning · Statistics 2018-06-12 Marta M. Stepniewska-Dziubinska , Piotr Zielenkiewicz , Pawel Siedlecki

Protein-ligand binding prediction is central to virtual screening and affinity ranking, two fundamental tasks in drug discovery. While recent retrieval-based methods embed ligands and protein pockets into Euclidean space for…

Machine Learning · Computer Science 2025-11-25 Jianhui Wang , Wenyu Zhu , Bowen Gao , Xin Hong , Ya-Qin Zhang , Wei-Ying Ma , Yanyan Lan

Accurate prediction of protein-ligand binding affinity is crucial for rapid and efficient drug development. Recently, the importance of predicting binding affinity has led to increased attention on research that models the three-dimensional…

Machine Learning · Computer Science 2024-07-17 Seungyeon Choi , Sangmin Seo , Sanghyun Park

Accurate estimation of mutational effects on protein-protein binding energies is an open problem with applications in structural biology and therapeutic design. Several deep learning predictors for this task have been proposed, but,…

Biomolecules · Quantitative Biology 2025-07-09 Arthur Deng , Karsten Householder , Fang Wu , Sebastian Thrun , K. Christopher Garcia , Brian Trippe

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

Motivation: Ab initio protein docking represents a major challenge for optimizing a noisy and costly "black box"-like function in a high-dimensional space. Despite progress in this field, there is no docking method available for rigorous…

Biomolecules · Quantitative Biology 2019-02-04 Yue Cao , Yang Shen

In recent years, advances in artificial intelligence (AI) have transformed structural biology, particularly protein structure prediction. Though AI-based methods, such as AlphaFold (AF), often predict single conformations of proteins with…

Biomolecules · Quantitative Biology 2024-10-22 Devlina Chakravarty , Myeongsang Lee , Lauren L. Porter

A protein's function depends critically on its conformational ensemble, a collection of energy weighted structures whose balance depends on temperature and environment. Though recent deep learning (DL) methods have substantially advanced…

Biomolecules · Quantitative Biology 2026-01-09 Myeongsang Lee , Lauren L. Porter

The process of screening molecules for desirable properties is a key step in several applications, ranging from drug discovery to material design. During the process of drug discovery specifically, protein-ligand docking, or chemical…

Machine Learning · Computer Science 2022-11-08 Ryien Hosseini , Filippo Simini , Austin Clyde , Arvind Ramanathan

Proteins are the basic building blocks of life. They usually perform functions by folding to a particular structure. Understanding the folding process could help the researchers to understand the functions of proteins and could also help to…

Computational Engineering, Finance, and Science · Computer Science 2015-10-21 Jianzhu Ma

We explored the Protein DataBank (PDB) to collect protein-ssDNA structures and create a multiconformational docking benchmark including both bound and unbound protein structures. Due to ssDNA high flexibility when not bound, no ssDNA…

Quantitative Methods · Quantitative Biology 2022-10-21 Dominique Mias-Lucquin , Isaure Chauvot de Beauchene

Deep learning promises to dramatically improve scoring functions for molecular docking, leading to substantial advances in binding pose prediction and virtual screening. To train scoring functions-and to perform molecular docking-one must…

Biomolecules · Quantitative Biology 2023-12-04 Patricia Suriana , Ron O. Dror

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

We have earlier reported the iMOLSDOCK technique to perform induced-fit peptide-protein docking. iMOLSDOCK uses the mutually orthogonal Latin squares (MOLS) technique to sample the conformation and the docking pose of the small molecule…

Biological Physics · Physics 2020-10-13 D. Sam Paul , N. Gautham

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

Side chain flexibility is an important factor in ligand binding. In order to determine the extent to which side chain flexibility is involved in ligand binding, a knowledge-based approach was taken. A database composed of examples of…

Biomolecules · Quantitative Biology 2013-01-22 Rafael Najmanovich

Identifying drug-target interactions is essential for developing effective therapeutics. Binding affinity quantifies these interactions, and traditional approaches rely on computationally intensive 3D structural data. In contrast, language…

Quantitative Methods · Quantitative Biology 2024-11-08 Radheesh Sharma Meda , Amir Barati Farimani

Motivation: Identification of flexible regions of protein structures is important for understanding of their biological functions. Recently, we have developed a fast approach for predicting protein structure fluctuations from a single…

Biomolecules · Quantitative Biology 2014-08-19 Michal Jamroz , Andrzej Kolinski , Sebastian Kmiecik

The knowledge of potentially druggable binding sites on proteins is an important preliminary step towards the discovery of novel drugs. The computational prediction of such areas can be boosted by following the recent major advances in the…

Biomolecules · Quantitative Biology 2021-02-17 Stelios K. Mylonas , Apostolos Axenopoulos , Petros Daras
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