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De novo molecular design has facilitated the exploration of large chemical space to accelerate drug discovery. Structure-based de novo method can overcome the data scarcity of active ligands by incorporating drug-target interaction into…

Biomolecules · Quantitative Biology 2022-09-16 Yaqin Li , Lingli Li , Yongjin Xu , Yi Yu

Direct Preference Optimization (DPO) has been proposed as an effective and efficient alternative to reinforcement learning from human feedback (RLHF). However, neither RLHF nor DPO take into account the fact that learning certain…

Computer Vision and Pattern Recognition · Computer Science 2026-02-16 Florinel-Alin Croitoru , Vlad Hondru , Radu Tudor Ionescu , Nicu Sebe , Mubarak Shah

Aligning large language models with human preferences is crucial for their safe deployment. While Direct Preference Optimization (DPO) offers an efficient alternative to reinforcement learning from human feedback, traditional DPO methods…

Artificial Intelligence · Computer Science 2025-07-30 Mengyang Li , Zhong Zhang

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

Direct Preference Optimization (DPO) has been proposed as an effective and efficient alternative to reinforcement learning from human feedback (RLHF). In this paper, we propose a novel and enhanced version of DPO based on curriculum…

Computer Vision and Pattern Recognition · Computer Science 2025-05-12 Florinel-Alin Croitoru , Vlad Hondru , Radu Tudor Ionescu , Nicu Sebe , Mubarak Shah

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

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

Lead optimization in drug discovery requires efficiently navigating vast chemical space through iterative cycles to enhance molecular properties while preserving structural similarity to the original lead compound. Despite recent advances,…

Machine Learning · Computer Science 2025-09-29 Ziqing Wang , Yibo Wen , William Pattie , Xiao Luo , Weimin Wu , Jerry Yao-Chieh Hu , Abhishek Pandey , Han Liu , Kaize Ding

Developing new drugs is laborious and costly, demanding extensive time investment. In this paper, we introduce a de-novo drug design strategy, which harnesses the capabilities of language models to devise targeted drugs for specific…

Biomolecules · Quantitative Biology 2025-05-20 Salma J. Ahmed , Emad A. Mohammed

De novo drug design is a pivotal issue in pharmacology and a new area of focus in AI for science research. A central challenge in this field is to generate molecules with specific properties while also producing a wide range of diverse…

Biomolecules · Quantitative Biology 2024-01-15 Xiuyuan Hu , Guoqing Liu , Yang Zhao , Hao Zhang

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

De novo design seeks to generate molecules with required property profiles by virtual design-make-test cycles. With the emergence of deep learning and neural generative models in many application areas, models for molecular design based on…

Quantitative Methods · Quantitative Biology 2021-01-05 Nathan Brown , Marco Fiscato , Marwin H. S. Segler , Alain C. Vaucher

Neural retrieval models excel in Web search, but their training requires substantial amounts of labeled query-document pairs, which are costly to obtain. With the widespread availability of Web document collections like ClueWeb22, synthetic…

Information Retrieval · Computer Science 2025-05-27 João Coelho , Bruno Martins , João Magalhães , Chenyan Xiong

Direct Preference Optimization (DPO) has become a widely used training method for the instruction fine-tuning of large language models (LLMs). In this work, we explore an under-investigated aspect of DPO - its dependency on the reference…

Computation and Language · Computer Science 2024-08-23 Yixin Liu , Pengfei Liu , Arman Cohan

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

Radiography Report Generation (RRG) has gained significant attention in medical image analysis as a promising tool for alleviating the growing workload of radiologists. However, despite numerous advancements, existing methods have yet to…

Computer Vision and Pattern Recognition · Computer Science 2025-09-29 Valentin Samokhin , Boris Shirokikh , Mikhail Goncharov , Dmitriy Umerenkov , Maksim Bobrin , Ivan Oseledets , Dmitry Dylov , Mikhail Belyaev

While reinforcement learning methods such as Group Relative Preference Optimization (GRPO) have significantly enhanced Large Language Models, adapting them to diffusion models remains challenging. In particular, GRPO demands a stochastic…

Machine Learning · Computer Science 2025-10-10 Yihong Luo , Tianyang Hu , Jing Tang

Direct Preference Optimization (DPO) is an effective technique that leverages pairwise preference data (usually one chosen and rejected response pair per user prompt) to align LLMs to human preferences. In practice, multiple responses can…

Computation and Language · Computer Science 2024-11-11 Pulkit Pattnaik , Rishabh Maheshwary , Kelechi Ogueji , Vikas Yadav , Sathwik Tejaswi Madhusudhan

Direct Preference Optimization (DPO) have emerged as a popular method for aligning Large Language Models (LLMs) with human preferences. While DPO effectively preserves the relative ordering between chosen and rejected responses through…

Computation and Language · Computer Science 2025-06-05 Lin Sun , Chuang Liu , Peng Liu , Bingyang Li , Weijia Lu , Ning Wu

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
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