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Protein-ligand interactions are one of the fundamental types of molecular interactions in living systems. Ligands are small molecules that interact with protein molecules at specific regions on their surfaces called binding sites. Tasks…

Biomolecules · Quantitative Biology 2020-08-11 Arnab Bhadra , Kalidas Y

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

Accurate protein structures are essential for understanding biological function, yet incorporating experimental data into protein generative models remains a major challenge. Most predictors of experimental observables are…

Machine Learning · Computer Science 2025-11-18 Nadav Bojan Sellam , Meital Bojan , Paul Schanda , Alex Bronstein

The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction,…

Biomolecules · Quantitative Biology 2022-11-28 Kevin E. Wu , Kevin K. Yang , Rianne van den Berg , James Y. Zou , Alex X. Lu , Ava P. Amini

In this work we present a system based on a Deep Learning approach, by using a Convolutional Neural Network, capable of classifying protein chains of amino acids based on the protein description contained in the Protein Data Bank. Each…

Machine Learning · Computer Science 2021-11-04 Damiano Perri , Marco Simonetti , Andrea Lombardi , Noelia Faginas-Lago , Osvaldo Gervasi

Drug discovery represents a time-consuming and financially intensive process, and virtual screening can accelerate it. Scoring functions, as one of the tools guiding virtual screening, have their precision closely tied to screening…

Machine Learning · Computer Science 2026-01-13 Haotian Gao , Xiangying Zhang , Jingyuan Li , Xinchong Chen , Haojie Wang , Yifei Qi , Renxiao Wang

Proteins are essential macromolecules defined by their amino acid sequences, which determine their three-dimensional structures and, consequently, their functions in all living organisms. Therefore, generative protein modeling necessitates…

Machine Learning · Computer Science 2024-10-18 Xinyou Wang , Zaixiang Zheng , Fei Ye , Dongyu Xue , Shujian Huang , Quanquan Gu

Deep learning has achieved tremendous success in designing novel chemical compounds with desirable pharmaceutical properties. In this work, we focus on a new type of drug design problem -- generating a small "linker" to physically attach…

Machine Learning · Computer Science 2022-05-17 Yinan Huang , Xingang Peng , Jianzhu Ma , Muhan Zhang

Computational drug discovery provides an efficient tool helping large scale lead molecules screening. One of the major tasks of lead discovery is identifying molecules with promising binding affinities towards a target, a protein in…

Biological Physics · Physics 2019-09-18 Liangzhen Zheng , Jingrong Fan , Yuguang Mu

We study a fundamental problem in structure-based drug design -- generating molecules that bind to specific protein binding sites. While we have witnessed the great success of deep generative models in drug design, the existing methods are…

Biomolecules · Quantitative Biology 2022-11-15 Shitong Luo , Jiaqi Guan , Jianzhu Ma , Jian Peng

The biological properties of proteins are uniquely determined by their structure and dynamics. A protein in solution populates a structural ensemble of metastable configurations around the global fold. From overall rotation to local…

Biological Physics · Physics 2015-12-09 J. Copperman , M. G. Guenza

Structure determination is key to understanding protein function at a molecular level. Whilst significant advances have been made in predicting structure and function from amino acid sequence, researchers must still rely on expensive,…

Computer Vision and Pattern Recognition · Computer Science 2020-09-01 Alexander Hudson , Shaogang Gong

Protein structure prediction and folding are fundamental to understanding biology, with recent deep learning advances reshaping the field. Diffusion-based generative models have revolutionized protein design, enabling the creation of novel…

Machine Learning · Computer Science 2025-10-01 Yogesh Verma , Markus Heinonen , Vikas Garg

Computational approaches to drug discovery can reduce the time and cost associated with experimental assays and enable the screening of novel chemotypes. Structure-based drug design methods rely on scoring functions to rank and predict…

Machine Learning · Statistics 2020-10-19 Matthew Ragoza , Joshua Hochuli , Elisa Idrobo , Jocelyn Sunseri , David Ryan Koes

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

Motivation: Protein folding is a dynamic process during which a protein's amino acid sequence undergoes a series of 3-dimensional (3D) conformational changes en route to reaching a native 3D structure; the resulting 3D structural…

Biomolecules · Quantitative Biology 2026-04-09 Aydin Wells , Khalique Newaz , Jennifer Morones , Jianlin Cheng , Tijana Milenković

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

Accurately predicting the binding conformation of small-molecule ligands to protein targets is a critical step in rational drug design. Although recent deep learning-based docking surpasses traditional methods in speed and accuracy, many…

Computer Vision and Pattern Recognition · Computer Science 2025-08-14 Liyan Jia , Chuan-Xian Ren , Hong Yan

Proteins perform much of the work in living organisms, and consequently the development of efficient computational methods for protein representation is essential for advancing large-scale biological research. Most current approaches…

Quantitative Methods · Quantitative Biology 2023-06-09 Francesco Ceccarelli , Lorenzo Giusti , Sean B. Holden , Pietro Liò

Finding drug-like compounds with high bioactivity is essential for drug discovery, but the task is complicated by the high cost of chemical synthesis and validation. With their outstanding performance in de novo drug design, deep generative…

Quantitative Methods · Quantitative Biology 2023-01-03 Yibo Li , Jianfeng Pei , Luhua Lai