English
Related papers

Related papers: A Variational Perspective on Generative Protein Fi…

200 papers

Direct Preference Optimization (DPO) is an effective approach for aligning protein language models with experimental design goals. However, DPO faces a scalability bottleneck: the number of possible training pairs grows quadratically with…

Machine Learning · Computer Science 2025-11-27 Constance Ferragu , Jonathan D. Ziegler , Nicolas Deutschmann , Arthur Lindoulsi , Eli Bixby , Cradle ML Team

Recent advances in large language models have highlighted the critical need for precise control over model outputs through predefined constraints. While existing methods attempt to achieve this through either direct instruction-response…

Computation and Language · Computer Science 2025-03-27 Zhouhong Gu , Xingzhou Chen , Xiaoran Shi , Tao Wang , Suhang Zheng , Tianyu Li , Hongwei Feng , Yanghua Xiao

Large-scale video diffusion models achieve impressive visual quality, yet often fail to preserve geometric consistency. Prior approaches improve consistency either by augmenting the generator with additional modules or applying…

Computer Vision and Pattern Recognition · Computer Science 2026-03-30 Zhaochong An , Orest Kupyn , Théo Uscidda , Andrea Colaco , Karan Ahuja , Serge Belongie , Mar Gonzalez-Franco , Marta Tintore Gazulla

Protein language models have emerged as powerful tools for sequence generation, offering substantial advantages in functional optimization and denovo design. However, these models also present significant risks of generating harmful protein…

Artificial Intelligence · Computer Science 2025-07-16 Yuhao Wang , Keyan Ding , Kehua Feng , Zeyuan Wang , Ming Qin , Xiaotong Li , Qiang Zhang , Huajun Chen

Protein structure prediction can be shown to be an NP-hard problem; the number of conformations grows exponentially with the number of residues. The native conformations of proteins occupy a very small subset of these, hence an exploratory,…

Chemical Physics · Physics 2008-02-03 Mehul M. Khimasia , Peter V. Coveney

Aligning denoising generative models with human preferences or verifiable rewards remains a key challenge. While policy-gradient online reinforcement learning (RL) offers a principled post-training framework, its direct application is…

Machine Learning · Computer Science 2026-04-28 Bingda Tang , Yuhui Zhang , Xiaohan Wang , Jiayuan Mao , Ludwig Schmidt , Serena Yeung-Levy

Directed evolution is a versatile technique in protein engineering that mimics the process of natural selection by iteratively alternating between mutagenesis and screening in order to search for sequences that optimize a given property of…

Biomolecules · Quantitative Biology 2024-05-02 Lixue Cheng , Ziyi Yang , Changyu Hsieh , Benben Liao , Shengyu Zhang

Protein fitness optimization is inherently a discrete combinatorial problem, yet most learning-based approaches rely on continuous representations and are primarily evaluated through predictive accuracy. We introduce Q-BIOLAT, a framework…

Machine Learning · Computer Science 2026-03-31 Truong-Son Hy

We propose Q-BIOLAT, a framework for modeling and optimizing protein fitness landscapes in binary latent spaces. Starting from protein sequences, we leverage pretrained protein language models to obtain continuous embeddings, which are then…

Machine Learning · Computer Science 2026-03-19 Truong-Son Hy

When governed by underlying low-dimensional dynamics, the interdependence of simultaneously recorded population of neurons can be explained by a small number of shared factors, or a low-dimensional trajectory. Recovering these latent…

Machine Learning · Statistics 2017-04-20 Yuan Zhao , Il Memming Park

Designing novel functional proteins remains a slow and expensive process due to a variety of protein engineering challenges; in particular, the number of protein variants that can be experimentally tested in a given assay pales in…

Quantitative Methods · Quantitative Biology 2023-05-29 M. Zaki Jawaid , Robin W. Yeo , Aayushma Gautam , T. Blair Gainous , Daniel O. Hart , Timothy P. Daley

Generative modeling has become a central paradigm in protein research, extending machine learning beyond structure prediction toward sequence design, backbone generation, inverse folding, and biomolecular interaction modeling. However, the…

Machine Learning · Computer Science 2026-03-30 Senura Hansaja Wanasekara , Minh-Duong Nguyen , Xiaochen Liu , Nguyen H. Tran , Ken-Tye Yong

Protein design aims to compose amino-acid sequences that fold into stable three-dimensional structures while satisfying targeted functional properties. The field is increasingly shifting toward vibe protein design, where a single model is…

Protein function does not solely depend on structure but often relies on dynamical transitions between distinct conformations. Despite this fact, our ability to characterize or predict protein dynamics is substantially less developed…

Statistical Mechanics · Physics 2026-05-08 Michael A. Sauer , Souvik Mondal , Brandon Neff , Sthitadhi Maiti , Matthias Heyden

Designing protein sequences of both high fitness and novelty is a challenging task in data-efficient protein engineering. Exploration beyond wild-type neighborhoods often leads to biologically implausible sequences or relies on surrogate…

Machine Learning · Computer Science 2025-10-28 Michal Kmicikiewicz , Vincent Fortuin , Ewa Szczurek

Proton therapy is a modality in fast development. Characterized by a maximum dose deposition at the end of the proton trajectory followed by a sharp fall-off, proton beams can deliver a highly conformal dose to the tumor while sparing…

Medical Physics · Physics 2022-05-18 François Smekens , Nicolas Freud , Bruno Sixou , Guillaume Beslon , Jean M Létang

The design of novel protein sequences with targeted functionalities underpins a central theme in protein engineering, impacting diverse fields such as drug discovery and enzymatic engineering. However, navigating this vast combinatorial…

Biomolecules · Quantitative Biology 2024-02-19 Yiheng Zhu , Zitai Kong , Jialu Wu , Weize Liu , Yuqiang Han , Mingze Yin , Hongxia Xu , Chang-Yu Hsieh , Tingjun Hou

Protein generative models have shown remarkable promise in protein design, yet their success rates remain constrained by reliance on curated sequence-structure datasets and by misalignment between supervised objectives and real design…

Machine Learning · Computer Science 2026-03-03 Ziwen Wang , Jiajun Fan , Ruihan Guo , Thao Nguyen , Heng Ji , Ge Liu

A popular approach to protein design is to combine a generative model with a discriminative model for conditional sampling. The generative model samples plausible sequences while the discriminative model guides a search for sequences with…

In evolutionary algorithms, the fitness of a population increases with time by mutating and recombining individuals and by a biased selection of more fit individuals. The right selection pressure is critical in ensuring sufficient…

Artificial Intelligence · Computer Science 2007-05-23 Marcus Hutter