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This paper introduces diffusion protein language model (DPLM), a versatile protein language model that demonstrates strong generative and predictive capabilities for protein sequences. We first pre-train scalable DPLMs from…

Machine Learning · Computer Science 2024-10-17 Xinyou Wang , Zaixiang Zheng , Fei Ye , Dongyu Xue , Shujian Huang , Quanquan Gu

Binding interactions between proteins and other molecules mediate numerous cellular processes, including metabolism, signaling, and regulation of gene expression. These interactions evolve in response to changes in the protein's chemical or…

Populations and Evolution · Quantitative Biology 2015-02-19 Michael Manhart , Alexandre V. Morozov

The function of biomolecules such as proteins depends on their ability to interconvert between a wide range of structures or "conformations." Researchers have endeavored for decades to develop computational methods to predict the…

Biomolecules · Quantitative Biology 2026-02-05 Daniel D. Richman , Jessica Karaguesian , Carl-Mikael Suomivuori , Ron O. Dror

This work examines the conformational ensemble involved in $\beta$-hairpin folding by means of advanced molecular dynamics simulations and dimensionality reduction. A fully atomistic description of the protein and the surrounding solvent…

Chemical Physics · Physics 2023-06-16 Albert Ardevol , Gareth A. Tribello , Michele Ceriotti , Michele Parrinello

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

Protein evolution underpins life, and understanding its behavior as a system is of great importance. However, our current models of protein evolution are arguably too simplistic to allow quantitative interpretation and prediction of…

Inverse protein folding, the process of designing sequences that fold into a specific 3D structure, is crucial in bio-engineering and drug discovery. Traditional methods rely on experimentally resolved structures, but these cover only a…

Biomolecules · Quantitative Biology 2023-11-27 Igor Melnyk , Aurelie Lozano , Payel Das , Vijil Chenthamarakshan

Predicting accurate protein-ligand binding affinity is important in drug discovery but remains a challenge even with computationally expensive biophysics-based energy scoring methods and state-of-the-art deep learning approaches. Despite…

Proteins need to selectively interact with specific targets among a multitude of similar molecules in the cell. But despite a firm physical understanding of binding interactions, we lack a general theory of how proteins evolve high…

Biomolecules · Quantitative Biology 2022-09-28 John M McBride , Jean-Pierre Eckmann , Tsvi Tlusty

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

Machine learning models of vastly different modalities and architectures are being trained to predict the behavior of molecules, materials, and proteins. However, it remains unclear whether they learn similar internal representations of…

Machine Learning · Computer Science 2025-12-04 Sathya Edamadaka , Soojung Yang , Ju Li , Rafael Gómez-Bombarelli

The protein folding problem has been fundamentally transformed by artificial intelligence, evolving from static structure prediction toward the modeling of dynamic conformational ensembles and complex biomolecular interactions. This review…

Computer Vision and Pattern Recognition · Computer Science 2026-03-20 Jingzhi Chen , Lijian Xu

Knowing the location of a protein within the cell is important for understanding its function, role in biological processes, and potential use as a drug target. Much progress has been made in developing computational methods that predict…

Quantitative Methods · Quantitative Biology 2013-08-02 Ramanuja Simha , Hagit Shatkay

After the recent ground-breaking advances in protein structure prediction, one of the remaining challenges in protein machine learning is to reliably predict distributions of structural states. Parametric models of fluctuations are…

Machine Learning · Computer Science 2024-01-25 Marloes Arts , Jes Frellsen , Wouter Boomsma

The classic paradigm of structural biology is that the sequence of a biomolecule (protein, nucleic acid, lipid, etc) determines its conformation (shape) which determines its biological function. Protein folding programs like AlphaFold…

Biomolecules · Quantitative Biology 2026-05-05 Alessio Valentini , David Pekker , Chungwen Liang , Todd Martinez , Swagatam Mukhopadhyay

The process of protein folding from an unfolded state to a biologically active, folded conformation is governed by many parameters e.g the sequence of amino acids, intermolecular interactions, the solvent, temperature and chaperon…

Soft Condensed Matter · Physics 2010-10-19 Pragya Shukla

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

Emergence of new protein structures has proved difficult to trace in nature and engineer in the laboratory. However, one aspect of structure evolution has proved immensely helpful for determining the three-dimensional structure of proteins…

Populations and Evolution · Quantitative Biology 2017-05-24 Amy I. Gilson , Ahmee Marshall-Christensen , Jeong-Mo Choi , Eugene I. Shakhnovich

Deep Learning and big data have shown tremendous success in bioinformatics and computational biology in recent years; artificial intelligence methods have also significantly contributed in the task of protein function classification. This…

Biomolecules · Quantitative Biology 2022-11-18 Divyanshu Aggarwal , Yasha Hasija

The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary…

Populations and Evolution · Quantitative Biology 2015-06-22 Mathieu Hemery , Olivier Rivoire