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Most protein families have fewer than 100 known members, a regime where deep generative models overfit or collapse. We propose stochastic attention (SA), a training-free sampler that treats the modern Hopfield energy over a protein…

Machine Learning · Computer Science 2026-03-17 Jeffrey D. Varner

We present a novel dual-head deep learning architecture for protein-protein interaction modeling that enables simultaneous prediction of binding affinity ($\Delta G$) and mutation-induced affinity changes ($\Delta\Delta G$) using only…

Quantitative Methods · Quantitative Biology 2025-09-30 Supantha Dey , Ratul Chowdhury

Models such as AlphaFold2 and OpenFold have transformed protein structure prediction, yet their inner workings remain poorly understood. We present a methodology to systematically evaluate the contribution of individual OpenFold components…

Biomolecules · Quantitative Biology 2025-11-20 Tyler L. Hayes , Giri P. Krishnan

Protein mutations can significantly influence protein solubility, which results in altered protein functions and leads to various diseases. Despite of tremendous effort, machine learning prediction of protein solubility changes upon…

Biomolecules · Quantitative Biology 2023-11-06 JunJie Wee , Jiahui Chen , Kelin Xia , Guo-Wei Wei

The inability to resolve deep node relationships of highly divergent/rapidly evolving protein families is a major factor that stymies evolutionary studies. In this manuscript, we propose a Multiple Sequence Alignment (MSA) independent…

Proteins play a vital role in biological processes and are indispensable for living organisms. Accurate representation of proteins is crucial, especially in drug development. Recently, there has been a notable increase in interest in…

Biomolecules · Quantitative Biology 2026-05-28 Dan Kalifa , Uriel Singer , Kira Radinsky

Recent advances in generative modeling show that pretrained representations can improve generation as conditioning features or alignment targets. Motivated by this, we study protein representations for predicting structures beyond…

Biomolecules · Quantitative Biology 2026-05-27 Taewon Kim , Hyosoon Jang , Hyunjin Seo , Seonghwan Seo , Hyeongwoo Kim , Wonho Zhung , Mingyeong Shin , Wooyoun Kim , Sungsoo Ahn

Fabricating neural models for a wide range of mobile devices demands for a specific design of networks due to highly constrained resources. Both evolution algorithms (EA) and reinforced learning methods (RL) have been dedicated to solve…

Neural and Evolutionary Computing · Computer Science 2019-01-17 Xiangxiang Chu , Bo Zhang , Ruijun Xu , Hailong Ma

Multi-output Gaussian process (MGP) is commonly used as a transfer learning method to leverage information among multiple outputs. A key advantage of MGP is providing uncertainty quantification for prediction, which is highly important for…

Machine Learning · Statistics 2024-09-06 Wang Xinming , Li Yongxiang , Yue Xiaowei , Wu Jianguo

The ability to accurately model the fitness landscape of protein sequences is critical to a wide range of applications, from quantifying the effects of human variants on disease likelihood, to predicting immune-escape mutations in viruses…

Machine Learning · Computer Science 2022-05-30 Pascal Notin , Mafalda Dias , Jonathan Frazer , Javier Marchena-Hurtado , Aidan Gomez , Debora S. Marks , Yarin Gal

Protein structure prediction models such as AlphaFold3 (AF3) push the frontier of biomolecular modeling by incorporating science-informed architectural changes to the transformer architecture. However, these advances come at a steep system…

Biomolecules · Quantitative Biology 2025-06-27 Hoa La , Ahan Gupta , Alex Morehead , Jianlin Cheng , Minjia Zhang

Generative models of macromolecules carry abundant and impactful implications for industrial and biomedical efforts in protein engineering. However, existing methods are currently limited to modeling protein structures or sequences,…

Biomolecules · Quantitative Biology 2024-01-15 Alex Morehead , Jeffrey Ruffolo , Aadyot Bhatnagar , Ali Madani

In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our…

Quantitative Methods · Quantitative Biology 2014-04-07 Carlo Baldassi , Marco Zamparo , Christoph Feinauer , Andrea Procaccini , Riccardo Zecchina , Martin Weigt , Andrea Pagnani

Multimodal Large Language Models (MLLMs) are widely regarded as crucial in the exploration of Artificial General Intelligence (AGI). The core of MLLMs lies in their capability to achieve cross-modal alignment. To attain this goal, current…

Computation and Language · Computer Science 2024-11-26 Fei Zhao , Taotian Pang , Chunhui Li , Zhen Wu , Junjie Guo , Shangyu Xing , Xinyu Dai

Proteins, as essential biomolecules, play a central role in biological processes, including metabolic reactions and DNA replication. Accurate prediction of their properties and functions is crucial in biological applications. Recent…

Computation and Language · Computer Science 2025-05-30 Wei Wu , Chao Wang , Liyi Chen , Mingze Yin , Yiheng Zhu , Kun Fu , Jieping Ye , Hui Xiong , Zheng Wang

Proteins are macromolecules that perform essential functions in all living organisms. Designing novel proteins with specific structures and desired functions has been a long-standing challenge in the field of bioengineering. Existing…

Biomolecules · Quantitative Biology 2023-03-03 Chence Shi , Chuanrui Wang , Jiarui Lu , Bozitao Zhong , Jian Tang

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…

Unraveling the dynamical motions of biomolecules is essential for bridging their structure and function, yet it remains a major computational challenge. Molecular dynamics (MD) simulation provides a detailed depiction of biomolecular…

Biomolecules · Quantitative Biology 2025-09-17 Allan dos Santos Costa , Manvitha Ponnapati , Dana Rubin , Tess Smidt , Joseph Jacobson

Motivation: Proteins are of great significance in living organisms. However, understanding their functions encounters numerous challenges, such as insufficient integration of multimodal information, a large number of training parameters,…

Machine Learning · Computer Science 2025-05-23 Zhicong Wang , Zicheng Ma , Ziqiang Cao , Changlong Zhou , Jun Zhang , Yiqin Gao

Computational prediction of membrane protein (MP) structures is very challenging partially due to lack of sufficient solved structures for homology modeling. Recently direct evolutionary coupling analysis (DCA) sheds some light on protein…

Biomolecules · Quantitative Biology 2017-05-11 Zhen Li , Sheng Wang , Yizhou Yu , Jinbo Xu