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Related papers: Protein Inverse Folding From Structure Feedback

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Inverse folding models play an important role in structure-based design by predicting amino acid sequences that fold into desired reference structures. Models like ProteinMPNN, a message-passing encoder-decoder model, are trained to…

Machine Learning · Computer Science 2026-05-12 Ryan Park , Darren J. Hsu , C. Brian Roland , Maria Korshunova , Chen Tessler , Shie Mannor , Olivia Viessmann , Bruno Trentini

Diffusion models have achieved promising results for Structure-Based Drug Design (SBDD). Nevertheless, high-quality protein subpocket and ligand data are relatively scarce, which hinders the models' generation capabilities. Recently, Direct…

Biomolecules · Quantitative Biology 2026-02-11 Xiwei Cheng , Xiangxin Zhou , Yuwei Yang , Yu Bao , Quanquan Gu

Designing protein sequences with optimal energetic stability is a key challenge in protein inverse folding, as current deep learning methods are primarily trained by maximizing sequence recovery rates, often neglecting the energy of the…

Machine Learning · Computer Science 2025-06-12 Dingyi Rong , Haotian Lu , Wenzhuo Zheng , Fan Zhang , Shuangjia Zheng , Ning Liu

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

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

Inverse protein folding -- the task of predicting a protein sequence from its backbone atom coordinates -- has surfaced as an important problem in the "top down", de novo design of proteins. Contemporary approaches have cast this problem as…

Direct Preference Optimisation (DPO) has emerged as a powerful method for aligning Large Language Models (LLMs) with human preferences, offering a stable and efficient alternative to approaches that use Reinforcement learning via Human…

Artificial Intelligence · Computer Science 2025-05-06 Sarvesh Shashidhar , Ritik , Nachiketa Patil , Suraj Racha , Ganesh Ramakrishnan

Inverse protein folding, the process of designing sequences that fold into a specific 3D structure, is crucial in bio-engineering and drug discovery. Traditional methods rely on experimentally resolved structures, but these cover only a…

Biomolecules · Quantitative Biology 2023-11-27 Igor Melnyk , Aurelie Lozano , Payel Das , Vijil Chenthamarakshan

Direct Preference Optimization (DPO) has become a popular approach for aligning language models using pairwise preferences. However, in practical post-training pipelines, on-policy generation typically yields multiple candidate responses…

Machine Learning · Computer Science 2025-06-23 Taneesh Gupta , Rahul Madhavan , Xuchao Zhang , Nagarajan Natarajan , Chetan Bansal , Saravan Rajmohan

This paper presents a method of reconstruction a primary structure of a protein that folds into a given geometrical shape. This method predicts the primary structure of a protein and restores its linear sequence of amino acids in the…

Quantitative Methods · Quantitative Biology 2017-01-04 Andrii Riazanov , Mikhail Karasikov , Sergei Grudinin

Direct Preference Optimization (DPO) has emerged as a de-facto approach for aligning language models with human preferences. Recent work has shown DPO's effectiveness relies on training data quality. In particular, clear quality differences…

Machine Learning · Computer Science 2025-01-28 Nirav Diwan , Tolga Ergen , Dongsub Shim , Honglak Lee

Designing RNA sequences that reliably adopt specified three-dimensional structures while maintaining thermodynamic stability remains challenging for synthetic biology and therapeutics. Current inverse folding approaches optimize for…

Protein inverse folding aims to design an amino acid sequence that will fold into a given backbone structure, serving as a central task in protein design. Two main paradigms have been widely explored. Template-based methods exploit…

Machine Learning · Computer Science 2026-03-17 Yiran Zhu , Changxi Chi , Hongxin Xiang , Wenjie Du , Xiaoqi Wang , Jun Xia

Recent alignment methods based on Direct Preference Optimization (DPO) reformulate preference learning as supervised optimization over pairwise comparisons, offering improved efficiency and stability over reinforcement learning from human…

Machine Learning · Computer Science 2026-01-22 Yuhui Sun , Xiyao Wang , Zixi Li , YiTian Ding , Tianyang Ling , Jialuo Chen , Tianyi Yu , Zhenlong Yuan , Jinman Zhao

The class of direct preference optimization (DPO) algorithms has emerged as a promising approach for solving the alignment problem in foundation models. These algorithms work with very limited feedback in the form of pairwise preferences…

Machine Learning · Computer Science 2026-02-03 Luca Viano , Ruida Zhou , Yifan Sun , Mahdi Namazifar , Volkan Cevher , Shoham Sabach , Mohammad Ghavamzadeh

We present a multi-objective binder design paradigm based on instruction fine-tuning and direct preference optimization (DPO) of autoregressive protein language models (pLMs). Multiple design objectives are encoded in the language model…

Biological Physics · Physics 2024-03-08 Pouria Mistani , Venkatesh Mysore

Iterative data generation and model retraining are widely used to align large language models (LLMs). It typically involves a policy model to generate on-policy responses and a reward model to guide training data selection. Direct…

Computation and Language · Computer Science 2025-07-01 Yao Xiao , Hai Ye , Linyao Chen , Hwee Tou Ng , Lidong Bing , Xiaoli Li , Roy Ka-wei Lee

Designing protein sequences that fold into a target 3D structure, known as protein inverse folding, is a fundamental challenge in protein engineering. While recent deep learning methods have achieved impressive performance by recovering…

Biomolecules · Quantitative Biology 2025-06-03 Mengdi Liu , Xiaoxue Cheng , Zhangyang Gao , Hong Chang , Cheng Tan , Shiguang Shan , Xilin Chen

DPO is an effective preference optimization algorithm. However, the DPO-tuned models tend to overfit on the dispreferred samples, manifested as overly long generations lacking diversity. While recent regularization approaches have…

Computation and Language · Computer Science 2025-08-26 Chenxu Yang , Ruipeng Jia , Naibin Gu , Zheng Lin , Siyuan Chen , Chao Pang , Weichong Yin , Yu Sun , Hua Wu , Weiping Wang

Direct preference optimization (DPO) is a successful fine-tuning strategy for aligning large language models with human preferences without the need to train a reward model or employ reinforcement learning. DPO, as originally formulated,…

Computation and Language · Computer Science 2024-06-07 Afra Amini , Tim Vieira , Ryan Cotterell
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