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A central problem in computational biophysics is protein structure prediction, i.e., finding the optimal folding of a given amino acid sequence. This problem has been studied in a classical abstract model, the HP model, where the protein is…

Machine Learning · Computer Science 2023-03-14 Kaiyuan Yang , Houjing Huang , Olafs Vandans , Adithya Murali , Fujia Tian , Roland H. C. Yap , Liang Dai

Inverse protein folding is challenging due to its inherent one-to-many mapping characteristic, where numerous possible amino acid sequences can fold into a single, identical protein backbone. This task involves not only identifying viable…

Quantitative Methods · Quantitative Biology 2023-11-08 Kai Yi , Bingxin Zhou , Yiqing Shen , Pietro Liò , Yu Guang Wang

Protein structure prediction is pivotal for understanding the structure-function relationship of proteins, advancing biological research, and facilitating pharmaceutical development and experimental design. While deep learning methods and…

Machine Learning · Computer Science 2024-12-30 Kaihui Cheng , Ce Liu , Qingkun Su , Jun Wang , Liwei Zhang , Yining Tang , Yao Yao , Siyu Zhu , Yuan Qi

Inverse Protein Folding (IPF) is a critical subtask in the field of protein design, aiming to engineer amino acid sequences capable of folding correctly into a specified three-dimensional (3D) conformation. Although substantial progress has…

Computation and Language · Computer Science 2025-05-20 Yanting Li , Jiyue Jiang , Zikang Wang , Ziqian Lin , Dongchen He , Yuheng Shan , Yanruisheng Shao , Jiayi Li , Xiangyu Shi , Jiuming Wang , Yanyu Chen , Yimin Fan , Han Li , Yu Li

Designing de novo 3D molecules with desirable properties remains a fundamental challenge in drug discovery and molecular engineering. While diffusion models have demonstrated remarkable capabilities in generating high-quality 3D molecular…

Machine Learning · Computer Science 2026-01-15 Lianghong Chen , Dongkyu Eugene Kim , Mike Domaratzki , Pingzhao Hu

Protein language models (pLMs) have demonstrated success at generating functional proteins across vast sequence spaces but lack the ability to design high-fitness variants on demand. Here, we iteratively guide pLMs toward user-defined…

Biomolecules · Quantitative Biology 2025-12-01 Filippo Stocco , Maria Artigues-Lleixa , Andrea Hunklinger , Talal Widatalla , Marc Guell , Noelia Ferruz

Despite considerable progress, ab initio protein structure prediction remains suboptimal. A crowdsourcing approach is the online puzzle video game Foldit, that provided several useful results that matched or even outperformed…

Biomolecules · Quantitative Biology 2020-11-09 Dimitra N. Panou , Martin Reczko

Construction of a scaffold structure that supports a desired motif, conferring protein function, shows promise for the design of vaccines and enzymes. But a general solution to this motif-scaffolding problem remains open. Current…

Biomolecules · Quantitative Biology 2023-03-21 Brian L. Trippe , Jason Yim , Doug Tischer , David Baker , Tamara Broderick , Regina Barzilay , Tommi Jaakkola

This tutorial provides a comprehensive survey of methods for fine-tuning diffusion models to optimize downstream reward functions. While diffusion models are widely known to provide excellent generative modeling capability, practical…

Machine Learning · Computer Science 2024-07-19 Masatoshi Uehara , Yulai Zhao , Tommaso Biancalani , Sergey Levine

It is commonly believed that optimizing the reverse KL divergence results in "mode seeking", while optimizing forward KL results in "mass covering", with the latter being preferred if the goal is to sample from multiple diverse modes. We…

Machine Learning · Computer Science 2025-10-24 Anthony GX-Chen , Jatin Prakash , Jeff Guo , Rob Fergus , Rajesh Ranganath

The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction,…

Biomolecules · Quantitative Biology 2022-11-28 Kevin E. Wu , Kevin K. Yang , Rianne van den Berg , James Y. Zou , Alex X. Lu , Ava P. Amini

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…

In order to speed-up classification models when facing a large number of categories, one usual approach consists in organizing the categories in a particular structure, this structure being then used as a way to speed-up the prediction…

Machine Learning · Computer Science 2015-11-26 Aurélia Léon , Ludovic Denoyer

Reinforcement Learning (RL), bolstered by the expressive capabilities of Deep Neural Networks (DNNs) for function approximation, has demonstrated considerable success in numerous applications. However, its practicality in addressing various…

Machine Learning · Computer Science 2024-04-26 Aditya Mohan , Amy Zhang , Marius Lindauer

A new method for the identification of differential item functioning (DIF) by using recursive partitioning techniques is proposed. We assume an extension of the Rasch model that allows for DIF being induced by an arbitrary number of…

Methodology · Statistics 2015-02-17 Gerhard Tutz , Moritz Berger

Deep Learning has become interestingly popular in computer vision, mostly attaining near or above human-level performance in various vision tasks. But recent work has also demonstrated that these deep neural networks are very vulnerable to…

Machine Learning · Computer Science 2020-12-09 Shashi Kant Gupta

A protein's function depends critically on its conformational ensemble, a collection of energy weighted structures whose balance depends on temperature and environment. Though recent deep learning (DL) methods have substantially advanced…

Biomolecules · Quantitative Biology 2026-01-09 Myeongsang Lee , Lauren L. Porter

We consider the problem of antibody sequence design given 3D structural information. Building on previous work, we propose a fine-tuned inverse folding model that is specifically optimised for antibody structures and outperforms generic…

Biomolecules · Quantitative Biology 2023-10-31 Frédéric A. Dreyer , Daniel Cutting , Constantin Schneider , Henry Kenlay , Charlotte M. Deane

Proteins are essential for almost all biological processes and derive their diverse functions from complex 3D structures, which are in turn determined by their amino acid sequences. In this paper, we exploit the rich biological inductive…

Reinforcement learning (RL) struggles to scale to large, combinatorial action spaces common in many real-world problems. This paper introduces a novel framework for training discrete diffusion models as highly effective policies in these…

Machine Learning · Computer Science 2026-05-21 Haitong Ma , Ofir Nabati , Aviv Rosenberg , Bo Dai , Oran Lang , Craig Boutilier , Na Li , Shie Mannor , Lior Shani , Guy Tenneholtz