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During their evolution, proteins explore sequence space via an interplay between random mutations and phenotypic selection. Here we build upon recent progress in reconstructing data-driven fitness landscapes for families of homologous…

Biomolecules · Quantitative Biology 2022-01-28 Matteo Bisardi , Juan Rodriguez-Rivas , Francesco Zamponi , Martin Weigt

We address the problem of learning on sets of features, motivated by the need of performing pooling operations in long biological sequences of varying sizes, with long-range dependencies, and possibly few labeled data. To address this…

Machine Learning · Computer Science 2021-02-11 Grégoire Mialon , Dexiong Chen , Alexandre d'Aspremont , Julien Mairal

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

We present a new method for design problems wherein the goal is to maximize or specify the value of one or more properties of interest. For example, in protein design, one may wish to find the protein sequence that maximizes fluorescence.…

Machine Learning · Computer Science 2021-05-13 David H. Brookes , Hahnbeom Park , Jennifer Listgarten

Guidance provides a simple and effective framework for posterior sampling by steering the generation process towards the desired distribution. When modeling discrete data, existing approaches mostly focus on guidance with the first-order…

Machine Learning · Computer Science 2026-04-16 Zhengyan Wan , Yidong Ouyang , Liyan Xie , Fang Fang , Hongyuan Zha , Guang Cheng

Proteins are fundamental to biology, executing diverse functions through complex physicochemical interactions, and they hold transformative potential across medicine, materials science, and environmental applications. Protein Language…

Biomolecules · Quantitative Biology 2025-06-11 Logan Hallee , Nikolaos Rafailidis , David B. Bichara , Jason P. Gleghorn

Bridging the exponentially growing gap between the numbers of unlabeled and labeled protein sequences, several studies adopted semi-supervised learning for protein sequence modeling. In these studies, models were pre-trained with a…

Biomolecules · Quantitative Biology 2021-09-20 Seonwoo Min , Seunghyun Park , Siwon Kim , Hyun-Soo Choi , Byunghan Lee , Sungroh Yoon

Biological machine learning is often bottlenecked by a lack of scaled data. One promising route to relieving data bottlenecks is through high throughput screens, which can experimentally test the activity of $10^6-10^{12}$ protein sequences…

Machine Learning · Statistics 2025-10-21 Eli N. Weinstein , Andrei Slabodkin , Mattia G. Gollub , Elizabeth B. Wood

Protein folding is a problem of large interest since it concerns the mechanism by which the genetic information is translated into proteins with well defined three-dimensional (3D) structures and functions. Recently theoretical models have…

Biomolecules · Quantitative Biology 2007-05-23 Emidio Capriotti , Rita Casadio

Protein sequence optimization under tight oracle budgets requires methods that explore vast combinatorial spaces while making each evaluation informative. Existing reinforcement learning and off-policy generative approaches often degrade…

Machine Learning · Computer Science 2026-05-27 Ashima Khanna , Dominik Grimm

Recent generative models have significantly advanced speech restoration tasks, yet their training objectives often misalign with human perceptual preferences, resulting in suboptimal quality. While post-training alignment has proven…

Sound · Computer Science 2025-11-18 Junan Zhang , Xueyao Zhang , Jing Yang , Yuancheng Wang , Fan Fan , Zhizheng Wu

Learning effective protein representations is critical in a variety of tasks in biology such as predicting protein functions. Recent sequence representation learning methods based on Protein Language Models (PLMs) excel in sequence-based…

Quantitative Methods · Quantitative Biology 2023-10-19 Zuobai Zhang , Chuanrui Wang , Minghao Xu , Vijil Chenthamarakshan , Aurélie Lozano , Payel Das , Jian Tang

Computational protein design is experiencing a transformation driven by AI/ML. However, the range of potential protein sequences and structures is astronomically vast, even for moderately sized proteins. Hence, achieving convergence between…

Distributed, Parallel, and Cluster Computing · Computer Science 2025-10-09 Aymen Alsaadi , Jonathan Ash , Mikhail Titov , Matteo Turilli , Andre Merzky , Shantenu Jha , Sagar Khare

We propose a novel approach for using unsupervised boosting to create an ensemble of generative models, where models are trained in sequence to correct earlier mistakes. Our meta-algorithmic framework can leverage any existing base learner…

Machine Learning · Computer Science 2017-12-25 Aditya Grover , Stefano Ermon

Despite recent advances, goal-directed generation of structured discrete data remains challenging. For problems such as program synthesis (generating source code) and materials design (generating molecules), finding examples which satisfy…

Machine Learning · Computer Science 2020-10-26 Amina Mollaysa , Brooks Paige , Alexandros Kalousis

Molecular dynamics (MD) is a powerful technique for studying microscopic phenomena, but its computational cost has driven significant interest in the development of deep learning-based surrogate models. We introduce generative modeling of…

Biomolecules · Quantitative Biology 2024-09-27 Bowen Jing , Hannes Stärk , Tommi Jaakkola , Bonnie Berger

Precise control over language model generation is vital for ensuring both safety and reliability. Although prompt engineering and steering are commonly used to intervene in model behaviors, the vast number of parameters in models often…

Computation and Language · Computer Science 2025-06-04 Mengru Wang , Ziwen Xu , Shengyu Mao , Shumin Deng , Zhaopeng Tu , Huajun Chen , Ningyu Zhang

Score-based generative models (SGMs) have proven to be powerful tools for designing new proteins. Designing proteins that bind a pre-specified target is highly relevant to a range of medical and industrial applications. Despite the flurry…

Biomolecules · Quantitative Biology 2024-09-30 John D Boom , Matthew Greenig , Pietro Sormanni , Pietro Liò

Proteins are dynamic, adopting ensembles of conformations. The nature of this conformational heterogenity is imprinted in the raw electron density measurements obtained from X-ray crystallography experiments. Fitting an ensemble of protein…

Quantitative Methods · Quantitative Biology 2024-12-19 Sai Advaith Maddipatla , Nadav Bojan Sellam , Sanketh Vedula , Ailie Marx , Alex Bronstein

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