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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

We present FLOWR.root, an SE(3)-equivariant flow-matching model for pocket-aware 3D ligand generation with joint potency and binding affinity prediction and confidence estimation. The model supports de novo generation, interaction- and…

Biomolecules · Quantitative Biology 2026-03-26 Julian Cremer , Tuan Le , Mohammad M. Ghahremanpour , Emilia Sługocka , Filipe Menezes , Djork-Arné Clevert

SE(3)-based generative models have shown great promise in protein geometry modeling and effective structure design. However, the field currently lacks a modularized benchmark to enable comprehensive investigation and fair comparison of…

Machine Learning · Computer Science 2025-07-29 Lang Yu , Zhangyang Gao , Cheng Tan , Qin Chen , Jie Zhou , Liang He

This study presents a conditional flow matching framework for solving physics-constrained Bayesian inverse problems. In this setting, samples from the joint distribution of inferred variables and measurements are assumed available, while…

Repeat proteins are made with tandem copies of similar amino acid stretches that fold into elongated architectures. Due to their symmetry, these proteins constitute excellent model systems to investigate how evolution relates to structure,…

Biomolecules · Quantitative Biology 2022-10-12 Ezequiel A. Galpern , Jacopo Marchi , Thierry Mora , Aleksandra M. Walczak , Diego U. Ferreiro

Flexibility is an intrinsic essential feature of protein structures, directly linked to their functions. To this day, most of the prediction methods use the crystallographic data (namely B-factors) as the only indicator of protein's inner…

We propose a new family of neural networks to predict the behaviors of physical systems by learning their underpinning constraints. A neural projection operator lies at the heart of our approach, composed of a lightweight network with an…

Neural and Evolutionary Computing · Computer Science 2020-12-15 Shuqi Yang , Xingzhe He , Bo Zhu

Many protein design applications, such as binder or enzyme design, require scaffolding a structural motif with high precision. Generative modelling paradigms based on denoising diffusion processes emerged as a leading candidate to address…

Machine Learning · Computer Science 2024-03-15 Kieran Didi , Francisco Vargas , Simon V Mathis , Vincent Dutordoir , Emile Mathieu , Urszula J Komorowska , Pietro Lio

The biological function of a protein stems from its 3-dimensional structure, which is thermodynamically determined by the energetics of interatomic forces between its amino acid building blocks (the order of amino acids, known as the…

Biomolecules · Quantitative Biology 2019-05-03 Sean Mullane , Ruoyan Chen , Sri Vaishnavi Vemulapalli , Eli J. Draizen , Ke Wang , Cameron Mura , Philip E. Bourne

Molecular docking that predicts the bound structures of small molecules (ligands) to their protein targets, plays a vital role in drug discovery. However, existing docking methods often face limitations: they either overlook crucial…

Quantitative Methods · Quantitative Biology 2025-02-24 Zizhuo Zhang , Lijun Wu , Kaiyuan Gao , Jiangchao Yao , Tao Qin , Bo Han

Computational protein design has the potential to deliver novel molecular structures, binders, and catalysts for myriad applications. Recent neural graph-based models that use backbone coordinate-derived features show exceptional…

Biomolecules · Quantitative Biology 2022-04-28 Alex J. Li , Vikram Sundar , Gevorg Grigoryan , Amy E. Keating

Computational protein design, i.e. inferring novel and diverse protein sequences consistent with a given structure, remains a major unsolved challenge. Recently, deep generative models that learn from sequences alone or from sequences and…

Biomolecules · Quantitative Biology 2021-11-15 Igor Melnyk , Payel Das , Vijil Chenthamarakshan , Aurelie Lozano

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

Unraveling the dynamical motions of biomolecules is essential for bridging their structure and function, yet it remains a major computational challenge. Molecular dynamics (MD) simulation provides a detailed depiction of biomolecular…

Biomolecules · Quantitative Biology 2025-09-17 Allan dos Santos Costa , Manvitha Ponnapati , Dana Rubin , Tess Smidt , Joseph Jacobson

Given native 2D contact map, protein 3D structure could be reconstructed with accuracy of 2A or better, and such reconstruction is a feasible computational approach for protein folding problem. The prediction accuracy from traditional…

Biomolecules · Quantitative Biology 2019-06-12 Yuhong Wang , Wei Li , Hongmao Sun , Kennie Cruz-Gutierrez

AlphaFold3 introduces a diffusion-based architecture that elevates protein structure prediction to all-atom resolution with improved accuracy. This state-of-the-art performance has established AlphaFold3 as a foundation model for diverse…

Machine Learning · Computer Science 2026-05-19 Zhe Zhang , Yuanning Feng , Yuxuan Song , Keyue Qiu , Hao Zhou , Wei-Ying Ma

The inverse design of microstructures plays a pivotal role in optimizing metamaterials with specific, targeted physical properties. While traditional forward design methods are constrained by their inability to explore the vast…

Computer Vision and Pattern Recognition · Computer Science 2025-02-06 Tianyang Xue , Haochen Li , Longdu Liu , Paul Henderson , Pengbin Tang , Lin Lu , Jikai Liu , Haisen Zhao , Hao Peng , Bernd Bickel

In this study, we expand upon the FLIP benchmark-designed for evaluating protein fitness prediction models in small, specialized prediction tasks-by assessing the performance of state-of-the-art large protein language models, including…

Machine Learning · Computer Science 2025-01-31 Manuel F. Mollon , Joaquin Gonzalez-Rodriguez , Alicia Lozano-Diez , Daniel Ramos , Doroteo T. Toledano

Morphing is a long-standing problem in vision and computer graphics, requiring a time-dependent warping for feature alignment and a blending for smooth interpolation. Recently, multilayer perceptrons (MLPs) have been explored as implicit…

Computer Vision and Pattern Recognition · Computer Science 2025-10-13 Arthur Bizzi , Matias Grynberg , Vitor Matias , Daniel Perazzo , João Paulo Lima , Luiz Velho , Nuno Gonçalves , João Pereira , Guilherme Schardong , Tiago Novello

While deep generative models show promise for learning inverse protein folding directly from data, the lack of publicly available structure-sequence pairings limits their generalization. Previous improvements and data augmentation efforts…

Artificial Intelligence · Computer Science 2024-07-23 Jiangbin Zheng , Stan Z. Li