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Identifying one or more biologically-active/native decoys from millions of non-native decoys is one of the major challenges in computational structural biology. The extreme lack of balance in positive and negative samples (native and…

Biomolecules · Quantitative Biology 2020-10-06 Nasrin Akhter , Gopinath Chennupati , Hristo Djidjev , Amarda Shehu

We discuss a stochastic approach for reconstructing the native structures of proteins from the knowledge of the "effective connectivity", which is a one-dimensional structural profile constructed as a linear combination of the eigenvectors…

Biological Physics · Physics 2009-01-20 Katrin Wolff , Michele Vendruscolo , Markus Porto

Protein structure prediction is considered as one of the most challenging and computationally intractable combinatorial problem. Thus, the efficient modeling of convoluted search space, the clever use of energy functions, and more…

Neural and Evolutionary Computing · Computer Science 2016-07-22 Mahmood A. Rashid , Sumaiya Iqbal , Firas Khatib , Md Tamjidul Hoque , Abdul Sattar

Accurate protein structures are essential for understanding biological function, yet incorporating experimental data into protein generative models remains a major challenge. Most predictors of experimental observables are…

Machine Learning · Computer Science 2025-11-18 Nadav Bojan Sellam , Meital Bojan , Paul Schanda , Alex Bronstein

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

Protein sequences are believed to have been selected to provide the stability of, and reliable renaturation to, an encoded unique spatial fold. In recently proposed theoretical schemes, this selection is modeled as ``minimal frustration,''…

Condensed Matter · Physics 2009-10-28 Vijay S. Pande , Alexander Yu. Grosberg , Toyoichi Tanaka

The advent of highly accurate protein structure prediction methods has fueled an exponential expansion of the protein structure database. Consequently, there is a rising demand for rapid and precise structural homolog search. Traditional…

Biomolecules · Quantitative Biology 2023-12-01 Yuan Liu , Hong-Bin Shen

For many membrane proteins the determination of their topology remains a challenge for methods like X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. Electron paramagnetic resonance (EPR) spectroscopy has evolved as…

Training energy-based models (EBMs) on discrete spaces is challenging because sampling over such spaces can be difficult. We propose to train discrete EBMs with energy discrepancy (ED), a novel type of contrastive loss functional which only…

Machine Learning · Statistics 2023-07-18 Tobias Schröder , Zijing Ou , Yingzhen Li , Andrew B. Duncan

Protein structure prediction and folding are fundamental to understanding biology, with recent deep learning advances reshaping the field. Diffusion-based generative models have revolutionized protein design, enabling the creation of novel…

Machine Learning · Computer Science 2025-10-01 Yogesh Verma , Markus Heinonen , Vikas Garg

The growing significance of RNA engineering in diverse biological applications has spurred interest in developing AI methods for structure-based RNA design. While diffusion models have excelled in protein design, adapting them for RNA…

Biomolecules · Quantitative Biology 2024-06-11 Divya Nori , Wengong Jin

Energy-Based Models (EBMs) assign unnormalized log-probability to data samples. This functionality has a variety of applications, such as sample synthesis, data denoising, sample restoration, outlier detection, Bayesian reasoning, and many…

Machine Learning · Statistics 2019-12-23 Zengyi Li , Yubei Chen , Friedrich T. Sommer

Significant progress in computer hardware and software have enabled molecular dynamics (MD) simulations to model complex biological phenomena such as protein folding. However, enabling MD simulations to access biologically relevant…

Biomolecules · Quantitative Biology 2019-08-02 Heng Ma , Debsindhu Bhowmik , Hyungro Lee , Matteo Turilli , Michael T. Young , Shantenu Jha , Arvind Ramanathan

Predictive models are highly advanced in understanding the mechanisms of brain function. Recent advances in machine learning further underscore the power of prediction for optimal representation in learning. However, there remains a gap in…

Machine Learning · Computer Science 2025-05-22 Xingsi Dong , Xiangyuan Peng , Si Wu

Effective representations of protein sequences are widely recognized as a cornerstone of machine learning-based protein design. Yet, protein bioengineering poses unique challenges for sequence representation, as experimental datasets…

Quantitative Methods · Quantitative Biology 2026-04-07 Ana F. Rodrigues , Lucas Ferraz , Laura Balbi , Pedro Giesteira Cotovio , Catia Pesquita

Decision-focused learning (DFL) was recently proposed for stochastic optimization problems that involve unknown parameters. By integrating predictive modeling with an implicitly differentiable optimization layer, DFL has shown superior…

Machine Learning · Computer Science 2022-11-28 Lingkai Kong , Jiaming Cui , Yuchen Zhuang , Rui Feng , B. Aditya Prakash , Chao Zhang

Inverse protein folding is a fundamental task in computational protein design, which aims to design protein sequences that fold into the desired backbone structures. While the development of machine learning algorithms for this task has…

Machine Learning · Computer Science 2024-11-05 Yiheng Zhu , Jialu Wu , Qiuyi Li , Jiahuan Yan , Mingze Yin , Wei Wu , Mingyang Li , Jieping Ye , Zheng Wang , Jian Wu

Proteins, essential to biological systems, perform functions intricately linked to their three-dimensional structures. Understanding the relationship between protein structures and their amino acid sequences remains a core challenge in…

Quantitative Methods · Quantitative Biology 2024-11-04 Liang He , Peiran Jin , Yaosen Min , Shufang Xie , Lijun Wu , Tao Qin , Xiaozhuan Liang , Kaiyuan Gao , Yuliang Jiang , Tie-Yan Liu

A new general algorithm for optimization of potential functions for protein folding is introduced. It is based upon gradient optimization of the thermodynamic stability of native folds of a training set of proteins with known structure. The…

Condensed Matter · Physics 2009-11-10 Ole Winther , Anders Krogh

Protein-ligand binding prediction is a fundamental problem in AI-driven drug discovery. Prior work focused on supervised learning methods using a large set of binding affinity data for small molecules, but it is hard to apply the same…

Biomolecules · Quantitative Biology 2023-12-14 Wengong Jin , Siranush Sarkizova , Xun Chen , Nir Hacohen , Caroline Uhler
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