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The evolutionary trajectory of a protein through sequence space is constrained by function and three-dimensional (3D) structure. Residues in spatial proximity tend to co-evolve, yet attempts to invert the evolutionary record to identify…

Biomolecules · Quantitative Biology 2015-03-13 Debora S. Marks , Lucy J. Colwell , Robert Sheridan , Thomas A. Hopf , Andrea Pagnani , Riccardo Zecchina , Chris Sander

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

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 Artificial Neural Network (ANN) models have demonstrated success in various domains, including general text and image generation, drug discovery, and protein-RNA (ribonucleic acid) binding tasks. However, these models typically demand…

Biomolecules · Quantitative Biology 2025-11-13 Stanislav Selitskiy

Protein-ligand binding prediction is a fundamental problem in AI-driven drug discovery. Prior work focused on supervised learning methods using a large set of binding affinity data for small molecules, but it is hard to apply the same…

Biomolecules · Quantitative Biology 2023-12-14 Wengong Jin , Siranush Sarkizova , Xun Chen , Nir Hacohen , Caroline Uhler

Free energy calculations are rapidly becoming indispensable in structure-enabled drug discovery programs. As new methods, force fields, and implementations are developed, assessing their expected accuracy on real-world systems…

The field of drug discovery hinges on the accurate prediction of binding affinity between prospective drug molecules and target proteins, especially when such proteins directly influence disease progression. However, estimating binding…

A pivotal area of research in antibody engineering is to find effective modifications that enhance antibody-antigen binding affinity. Traditional wet-lab experiments assess mutants in a costly and time-consuming manner. Emerging deep…

Quantitative Methods · Quantitative Biology 2025-05-28 Chen Liu , Mingchen Li , Yang Tan , Wenrui Gou , Guisheng Fan , Bingxin Zhou

The worldwide surge of multiresistant microbial strains has propelled the search for alternative treatment options. The study of Protein-Protein Interactions (PPIs) has been a cornerstone in the clarification of complex physiological and…

The accurate prediction of protein-RNA binding affinity remains an unsolved problem in structural biology, limiting opportunities in understanding gene regulation and designing RNA-targeting therapeutics. A central obstacle is the…

Predicting protein-protein interactions (PPIs) by learning informative representations from amino acid sequences is a challenging yet important problem in biology. Although various deep learning models in Siamese architecture have been…

Machine Learning · Computer Science 2020-10-19 Kishan KC , Feng Cui , Anne Haake , Rui Li

Determining the 3D structures of proteins is essential in understanding their behavior in the cellular environment. Computational methods of predicting protein structures have advanced, but assessing prediction accuracy remains a challenge.…

Biomolecules · Quantitative Biology 2024-07-29 Musa Azeem , Homayoun Valafar

We introduce a protein language model for determining the complete sequence of a peptide based on measurement of a limited set of amino acids. To date, protein sequencing relies on mass spectrometry, with some novel edman degregation based…

Accurately predicting protein structures from amino acid sequences remains a fundamental challenge in computational biology, with profound implications for understanding biological functions and enabling structure-based drug discovery.…

Predicting protein-ligand binding affinity remains intractable for multi-domain proteins, where inter-domain dynamics govern molecular recognition. Existing geometric deep learning methods typically treat proteins as monolithic static…

Machine Learning · Computer Science 2026-05-20 Shuo Zhang , Rongqi Hong , Huifeng Zhang , Jian K. Liu

Inferring the structural properties of a protein from its amino acid sequence is a challenging yet important problem in biology. Structures are not known for the vast majority of protein sequences, but structure is critical for…

Machine Learning · Computer Science 2019-10-17 Tristan Bepler , Bonnie Berger

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

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

The de novo design of ligand-binding proteins with tailored functions is essential for advancing biotechnology and molecular medicine, yet existing AI approaches are limited by scarce protein-ligand complex data. To circumvent this data…

Machine Learning · Computer Science 2026-03-03 Zhenqiao Song , Ramith Hettiarachchi , Chuan Li , Jianwen Xie , Lei Li

The amyloid state of proteins is widely studied with relevancy in neurology, biochemistry, and biotechnology. In contrast with amorphous aggregation, the amyloid state has a well-defined structure, consisting of parallel and anti-parallel…

Biomolecules · Quantitative Biology 2020-11-10 Laszlo Keresztes , Evelin Szogi , Balint Varga , Viktor Farkas , Andras Perczel , Vince Grolmusz
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