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Accurately modeling and designing protein complex structures is a central problem in computational structural biology, with broad implications for understanding cellular function and developing therapeutics. This thesis investigates two…

Machine Learning · Computer Science 2026-05-13 Ziwei Xie

By linking conceptual theories with observed data, generative models can support reasoning in complex situations. They have come to play a central role both within and beyond statistics, providing the basis for power analysis in molecular…

Methodology · Statistics 2022-08-15 Kris Sankaran , Susan P. Holmes

This review is a tutorial for scientists interested in the problem of protein structure prediction, particularly those interested in using coarse-grained molecular dynamics models that are optimized using lessons learned from the energy…

Biomolecules · Quantitative Biology 2014-01-06 N. P. Schafer , B. L. Kim , W. Zheng , P. G. Wolynes

Deep generative models have emerged as a powerful tool for learning useful molecular representations and designing novel molecules with desired properties, with applications in drug discovery and material design. However, most existing deep…

The binding complexes formed by proteins and small molecule ligands are ubiquitous and critical to life. Despite recent advancements in protein structure prediction, existing algorithms are so far unable to systematically predict the…

Quantitative Methods · Quantitative Biology 2023-04-21 Zhuoran Qiao , Weili Nie , Arash Vahdat , Thomas F. Miller , Anima Anandkumar

This chapter gives a graceful introduction to problem of protein three- dimensional structure prediction, and focuses on how to make structural sense out of a single input sequence with unknown structure, the 'query' or 'target' sequence.…

Biomolecules · Quantitative Biology 2017-12-04 Sanne Abeln , Jaap Heringa , K. Anton Feenstra

While many good textbooks are available on Protein Structure, Molecular Simulations, Thermodynamics and Bioinformatics methods in general, there is no good introductory level book for the field of Structural Bioinformatics. This book aims…

Recently described stochastic models of protein evolution have demonstrated that the inclusion of structural information in addition to amino acid sequences leads to a more reliable estimation of evolutionary parameters. We present a…

Populations and Evolution · Quantitative Biology 2020-09-22 Michael Golden , Eduardo García-Portugués , Michael Sørensen , Kanti V. Mardia , Thomas Hamelryck , Jotun Hein

Three-dimensional molecular structure generation is typically performed at the level of individual atoms, yet molecular graph generation techniques often consider fragments as their structural units. Building on the advances in frame-based…

Machine Learning · Computer Science 2026-01-26 Roman Poletukhin , Marcel Kollovieh , Eike Eberhard , Stephan Günnemann

The increasing number of protein sequences decoded from genomes is opening up new avenues of research on linking protein sequence to function with transformer neural networks. Recent research has shown that the number of known protein…

Machine Learning · Computer Science 2022-06-23 Anowarul Kabir , Amarda Shehu

While many good textbooks are available on Protein Structure, Molecular Simulations, Thermodynamics and Bioinformatics methods in general, there is no good introductory level book for the field of Structural Bioinformatics. This book aims…

We propose a novel interpretation technique to explain the behavior of structured output models, which learn mappings between an input vector to a set of output variables simultaneously. Because of the complex relationship between the…

Machine Learning · Computer Science 2025-08-12 S. Fatemeh Seyyedsalehi , Mahdieh Soleymani , Hamid R. Rabiee

Proteins are miniature machines whose function depends on their three-dimensional (3D) structure. Determining this structure computationally remains an unsolved grand challenge. A major bottleneck involves selecting the most accurate…

Quantitative Methods · Quantitative Biology 2020-11-30 Stephan Eismann , Patricia Suriana , Bowen Jing , Raphael J. L. Townshend , Ron O. Dror

Proteins are central to biological systems, participating as building blocks across all forms of life. Despite advancements in understanding protein functions through protein sequence analysis, there remains potential for further…

Machine Learning · Computer Science 2025-08-29 Yunqing Liu , Wenqi Fan , Xiaoyong Wei , Qing Li

Molecular dynamics (MD) is a powerful technique for studying microscopic phenomena, but its computational cost has driven significant interest in the development of deep learning-based surrogate models. We introduce generative modeling of…

Biomolecules · Quantitative Biology 2024-09-27 Bowen Jing , Hannes Stärk , Tommi Jaakkola , Bonnie Berger

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

Deep generative models show promise for $\textit{de novo}$ protein design, yet reliably producing designs that are geometrically plausible, evolutionarily consistent, functionally relevant, and dynamically stable remains challenging. We…

Biomolecules · Quantitative Biology 2025-07-15 Tianyuan Zheng , Alessandro Rondina , Gos Micklem , Pietro Liò

Graph-based representation approaches have been proven to be successful in the analysis of biomedical data, due to their capability of capturing intricate dependencies between biological entities, such as the spatial organization of…

Machine Learning · Computer Science 2023-10-11 Manuel Madeira , Dorina Thanou , Pascal Frossard

Generative machine learning models are increasingly being used to design novel proteins for therapeutic and biotechnological applications. However, the current methods mostly focus on the design of proteins with a fixed backbone structure,…

Biomolecules · Quantitative Biology 2025-03-04 Petr Kouba , Joan Planas-Iglesias , Jiri Damborsky , Jiri Sedlar , Stanislav Mazurenko , Josef Sivic

Although machine learning has been successfully used to propose novel molecules that satisfy desired properties, it is still challenging to explore a large chemical space efficiently. In this paper, we present a conditional molecular design…

Machine Learning · Computer Science 2019-04-02 Seokho Kang , Kyunghyun Cho
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