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We present PepEDiff, a novel peptide binder generator that designs binding sequences given a target receptor protein sequence and its pocket residues. Peptide binder generation is critical in therapeutic and biochemical applications, yet…

Artificial Intelligence · Computer Science 2026-03-09 Po-Yu Liang , Tibo Duran , Jun Bai

Molecule synthesis through machine learning is one of the fundamental problems in drug discovery. Current data-driven strategies employ one-step retrosynthesis models and search algorithms to predict synthetic routes in a top-bottom manner.…

Machine Learning · Computer Science 2024-06-05 Songtao Liu , Hanjun Dai , Yue Zhao , Peng Liu

Protein language models (pLMs) pre-trained on vast protein sequence databases excel at various downstream tasks but often lack the structural knowledge essential for some biological applications. To address this, we introduce a method to…

Energy-based models (EBMs) are powerful probabilistic models, but suffer from intractable sampling and density evaluation due to the partition function. As a result, inference in EBMs relies on approximate sampling algorithms, leading to a…

Machine Learning · Computer Science 2020-01-10 Dieterich Lawson , George Tucker , Bo Dai , Rajesh Ranganath

Designing protein-binding proteins with high affinity is critical in biomedical research and biotechnology. Despite recent advancements targeting specific proteins, the ability to create high-affinity binders for arbitrary protein targets…

Machine Learning · Computer Science 2025-11-03 Zhenqiao Song , Tiaoxiao Li , Lei Li , Martin Renqiang Min

Protein dynamics play a crucial role in protein biological functions and properties, and their traditional study typically relies on time-consuming molecular dynamics (MD) simulations conducted in silico. Recent advances in generative…

Biomolecules · Quantitative Biology 2025-06-02 Jiarui Lu , Xiaoyin Chen , Stephen Zhewen Lu , Aurélie Lozano , Vijil Chenthamarakshan , Payel Das , Jian Tang

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

Bond rating Transition Probability Matrices (TPMs) are built over a one-year time-frame and for many practical purposes, like the assessment of risk in portfolios or the computation of banking Capital Requirements (e.g. the new IFRS 9…

Risk Management · Quantitative Finance 2017-10-17 Greig Smith , Goncalo dos Reis

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

Predictive benchmarking, the evaluation of machine learning models based on predictive performance and competitive ranking, is a central epistemic practice in machine learning research and an increasingly prominent method for scientific…

Machine Learning · Computer Science 2025-10-28 Timo Freiesleben , Sebastian Zezulka

The demand for reliable AI systems has intensified the need for interpretable deep neural networks. Concept bottleneck models (CBMs) have gained attention as an effective approach by leveraging human-understandable concepts to enhance…

Computer Vision and Pattern Recognition · Computer Science 2024-09-24 Sangwon Kim , Dasom Ahn , Byoung Chul Ko , In-su Jang , Kwang-Ju Kim

Explainable boosting machines (EBMs) are popular "glass-box" models that learn a set of univariate functions using boosting trees. These achieve explainability through visualizations of each feature's effect. However, unlike linear model…

Machine Learning · Statistics 2026-03-31 Haimo Fang , Kevin Tan , Jonathan Pipping-Gamon , Giles Hooker

Tandem mass spectrometry provides a high-throughput framework for identifying and quantifying proteins in complex biological samples. In computational proteomics, predicting peptide MS/MS spectra is a critical task, enabling downstream…

Machine Learning · Computer Science 2026-05-05 Zhiwen Yang , Pan Liu , Yifan Li , Yunhua Zhong , Jun Xia

Proteins are biomolecules of life. They fold into a great variety of three-dimensional (3D) shapes. Underlying these folding patterns are many recurrent structural fragments or building blocks (analogous to `LEGO bricks'). This paper…

Quantitative Methods · Quantitative Biology 2013-10-08 Arun S. Konagurthu , Arthur M. Lesk , David Abramson , Peter J. Stuckey , Lloyd Allison

Protein binder design is central to therapeutics, diagnostics, and synthetic biology, yet practical deployment remains challenging due to fragmented workflows, high computational costs, and complex tool integration. We present…

Biomolecules · Quantitative Biology 2025-05-29 Jie Gao , Jun Li , Jing Hu , Shanzhuo Zhang , Kunrui Zhu , Yueyang Huang , Xiaonan Zhang , Xiaomin Fang

Engineering molecular systems that exhibit complex behavior requires the design of kinetic barriers. For example, an effective catalytic pathway must have a large barrier when the catalyst is absent. While programming such energy barriers…

Emerging Technologies · Computer Science 2020-01-28 Keenan Breik , Cameron Chalk , David Doty , David Haley , David Soloveichik

Click-through rate (CTR) prediction is a core task in recommender systems. Existing methods (IDRec for short) rely on unique identities to represent distinct users and items that have prevailed for decades. On one hand, IDRec often faces…

Information Retrieval · Computer Science 2024-03-18 Yuanbo Gao , Peng Lin , Dongyue Wang , Feng Mei , Xiwei Zhao , Sulong Xu , Jinghe Hu

Proteins are miniature machines whose function depends on their three-dimensional (3D) structure. Determining this structure computationally remains an unsolved grand challenge. A major bottleneck involves selecting the most accurate…

Quantitative Methods · Quantitative Biology 2020-11-30 Stephan Eismann , Patricia Suriana , Bowen Jing , Raphael J. L. Townshend , Ron O. Dror

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

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