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In the era of AI-driven science and engineering, we often want to design discrete objects in silico according to user-specified properties. For example, we may wish to design a protein to bind its target, arrange components within a circuit…

Machine Learning · Computer Science 2026-03-03 James C. Bowden , Sergey Levine , Jennifer Listgarten

Proteins are the fundamental macromolecules that play diverse and crucial roles in all living matter and have tremendous implications in healthcare, manufacturing, and biotechnology. Their functions are largely determined by the sequences…

Biomolecules · Quantitative Biology 2024-09-17 Boqiao Lai

Proteins perform critical processes in all living systems: converting solar energy into chemical energy, replicating DNA, as the basis of highly performant materials, sensing and much more. While an incredible range of functionality has…

Biomolecules · Quantitative Biology 2021-09-29 Leonardo V. Castorina , Rokas Petrenas , Kartic Subr , Christopher W. Wood

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

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…

Protein sequence design has seen significant advances through discrete diffusion and autoregressive approaches, yet the potential of continuous diffusion remains underexplored. Here, we present DiMA, a latent diffusion framework that…

Combinatorial Optimization (CO) problems are fundamentally important in numerous real-world applications across diverse industries, characterized by entailing enormous solution space and demanding time-sensitive response. Despite recent…

Artificial Intelligence · Computer Science 2025-06-10 Hang Zhao , Kexiong Yu , Yuhang Huang , Renjiao Yi , Chenyang Zhu , Kai Xu

Deep generative models that learn from the distribution of natural protein sequences and structures may enable the design of new proteins with valuable functions. While the majority of today's models focus on generating either sequences or…

Biomolecules · Quantitative Biology 2024-10-03 Chentong Wang , Sarah Alamdari , Carles Domingo-Enrich , Ava Amini , Kevin K. Yang

Computational protein design (CPD) offers transformative potential for bioengineering, but current deep CPD models, focused on universal domains, struggle with function-specific designs. This work introduces a novel CPD paradigm tailored…

Quantitative Methods · Quantitative Biology 2024-11-28 Jiangbin Zheng , Ge Wang , Han Zhang , Stan Z. Li

Building a general-purpose intelligent home-assistant agent skilled in diverse tasks by human commands is a long-term blueprint of embodied AI research, which poses requirements on task planning, environment modeling, and object…

Computer Vision and Pattern Recognition · Computer Science 2024-07-23 Xinyu Xu , Shengcheng Luo , Yanchao Yang , Yong-Lu Li , Cewu Lu

Proteins are macromolecules that mediate a significant fraction of the cellular processes that underlie life. An important task in bioengineering is designing proteins with specific 3D structures and chemical properties which enable…

Quantitative Methods · Quantitative Biology 2022-05-31 Namrata Anand , Tudor Achim

Evaluating modern machine learning models has become prohibitively expensive. Benchmarks such as LMMs-Eval and HELM demand thousands of GPU hours per model. Costly evaluation reduces inclusivity, slows the cycle of innovation, and worsens…

Machine Learning · Computer Science 2026-03-03 Alexander Rubinstein , Benjamin Raible , Martin Gubri , Seong Joon Oh

We address the problem of predicting the next state of a dynamical system governed by unknown temporal partial differential equations (PDEs) using only a short trajectory. While standard transformers provide a natural black-box solution to…

Machine Learning · Computer Science 2025-04-29 Rudy Morel , Jiequn Han , Edouard Oyallon

We present A-CODE, a fully atomic unified one-stage protein co-design model that simultaneously refines discrete atom types and continuous atom coordinates. Unlike predominant two-stage methods that cascade structure design with amino…

Quantitative Methods · Quantitative Biology 2026-05-06 Chaoran Cheng , Jiaqi Guan , Milong Ren , Chengyue Gong , Cong Liu , Xinshi Chen , Ge Liu , Wenzhi Xiao

Proteins are shaped by gradual evolution under biophysical and functional constraints. Protein language models learn rich evolutionary constraints from large-scale sequences, and discrete diffusion-based protein language models~(\eg, DPLMs)…

Machine Learning · Computer Science 2026-05-14 Xinyou Wang , Liang Hong , Jiasheng Ye , Zaixiang Zheng , Yu Li , Shujian Huang , Quanquan Gu

Protein design with desirable properties has been a significant challenge for many decades. Generative artificial intelligence is a promising approach and has achieved great success in various protein generation tasks. Notably, diffusion…

Protein sequence design methods have demonstrated strong performance in sequence generation for de novo protein design. However, as the training objective was sequence recovery, it does not guarantee designability--the likelihood that a…

Machine Learning · Computer Science 2025-06-03 Fanglei Xue , Andrew Kubaney , Zhichun Guo , Joseph K. Min , Ge Liu , Yi Yang , David Baker

Protein sequence design is a challenging problem in protein engineering, which aims to discover novel proteins with useful biological functions. Directed evolution is a widely-used approach for protein sequence design, which mimics the…

Machine Learning · Computer Science 2023-03-21 Chuanjiao Zong

Computational protein design facilitates discovery of novel proteins with prescribed structure and functionality. Exciting designs were recently reported using novel data-driven methodologies that can be roughly divided into two categories:…

Biological Physics · Physics 2023-03-28 Cyril Malbranke , David Bikard , Simona Cocco , Rémi Monasson , Jérôme Tubiana

Designing DNA and protein sequences with improved function has the potential to greatly accelerate synthetic biology. Machine learning models that accurately predict biological fitness from sequence are becoming a powerful tool for…

Machine Learning · Computer Science 2022-03-17 Johannes Linder , Georg Seelig
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