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We review the recent progress in computational approaches to protein design which builds on advances in statistical-mechanical protein folding theory. In particular, we evaluate the degeneracy of the protein code (i.e. how many sequences…

Condensed Matter · Physics 2007-05-23 E. I. Shakhnovich

Protein inverse folding aims to design an amino acid sequence that will fold into a given backbone structure, serving as a central task in protein design. Two main paradigms have been widely explored. Template-based methods exploit…

Machine Learning · Computer Science 2026-03-17 Yiran Zhu , Changxi Chi , Hongxin Xiang , Wenjie Du , Xiaoqi Wang , Jun Xia

Accurate prediction of protein-ligand binding poses is crucial for structure-based drug design, yet existing methods struggle to balance speed, accuracy, and physical plausibility. We introduce Matcha, a novel molecular docking pipeline…

The most popular and universally predictive protein simulation models employ all-atom molecular dynamics (MD), but they come at extreme computational cost. The development of a universal, computationally efficient coarse-grained (CG) model…

How proteins fold remains a central unsolved problem in biology. While the idea of a folding code embedded in the amino acid sequence was introduced more than 6 decades ago, this code remains undefined. While we now have powerful predictive…

Biomolecules · Quantitative Biology 2025-11-04 Carlos Bustamante , Christian Kaiser , Erik Lindahl , Robert Sosa , Giovanni Volpe

Nuclear magnetic relaxation is widely used to probe protein dynamics. For decades, most analyses of relaxation in proteins have relied successfully on the model-free approach, forgoing mechanistic descriptions of motions. Model-free types…

Computational prediction of enzymatic reactions represents a crucial challenge in sustainable chemical synthesis across various scientific domains, ranging from drug discovery to materials science and green chemistry. These syntheses rely…

Machine Learning · Computer Science 2025-02-04 Amitay Sicherman , Kira Radinsky

The design of novel proteins has many applications but remains an attritional process with success in isolated cases. Meanwhile, deep learning technologies have exploded in popularity in recent years and are increasingly applicable to…

Biomolecules · Quantitative Biology 2018-11-07 Joe G Greener , Lewis Moffat , David T Jones

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 learning has transformed protein design, enabling accurate structure prediction, sequence optimization, and de novo protein generation. Advances in single-chain protein structure prediction via AlphaFold2, RoseTTAFold, ESMFold, and…

Machine Learning · Computer Science 2025-02-27 Gregory W. Kyro , Tianyin Qiu , Victor S. Batista

The drug discovery process involves several tasks to be performed in vivo, in vitro and in silico. Molecular docking is a task typically performed in silico. It aims at finding the three-dimensional pose of a given molecule when it…

Distributed, Parallel, and Cluster Computing · Computer Science 2019-01-21 Davide Gadioli , Gianluca Palermo , Stefano Cherubin , Emanuele Vitali , Giovanni Agosta , Candida Manelfi , Andrea R. Beccari , Carlo Cavazzoni , Nico Sanna , Cristina Silvano

Virtual screening, including molecular docking, plays an essential role in drug discovery. Many traditional and machine-learning based methods are available to fulfil the docking task. The traditional docking methods are normally…

Chemical Physics · Physics 2023-03-20 YuPeng Huang , Hong Zhang , Siyuan Jiang , Dajiong Yue , Xiaohan Lin , Jun Zhang , Yi Qin Gao

Motivation: Ab initio protein docking represents a major challenge for optimizing a noisy and costly "black box"-like function in a high-dimensional space. Despite progress in this field, there is no docking method available for rigorous…

Biomolecules · Quantitative Biology 2019-02-04 Yue Cao , Yang Shen

Binding kinetic parameters can be correlated with drug efficacy, which led to the development of various computational methods for predicting binding kinetic rates and gaining insight into protein-drug binding paths and mechanisms in recent…

Biomolecules · Quantitative Biology 2022-09-27 Farzin Sohraby , Ariane Nunes-Alves

Selecting an effective docking algorithm is highly context-dependent, and no single method performs reliably across structural, chemical, or protocol regimes. We introduce MolAS, a lightweight algorithm selection system that predicts…

Quantitative Methods · Quantitative Biology 2025-12-03 Jiabao Brad Wang , Siyuan Cao , Hongxuan Wu , Yiliang Yuan , Mustafa Misir

In this paper we show that a dynamical description of the protein folding process provides an effective representation of equilibrium properties and it allows for a direct investigation of the mechanisms ruling the approach towards the…

Statistical Mechanics · Physics 2007-05-23 Alessandro Torcini , Roberto Livi , Antonio Politi

Protein activity is a significant characteristic for recombinant proteins which can be used as biocatalysts. High activity of proteins reduces the cost of biocatalysts. A model that can predict protein activity from amino acid sequence is…

Quantitative Methods · Quantitative Biology 2018-07-23 X. Han , X. Wang , K. Zhou

Intrinsically disordered proteins (IDPs) and multidomain proteins with flexible linkers show a high level of structural heterogeneity and are best described by ensembles consisting of multiple conformations with associated thermodynamic…

Biomolecules · Quantitative Biology 2021-12-13 F. Emil Thomasen , Kresten Lindorff-Larsen

The strength or weakness of an algorithm is ultimately governed by the confidence of its result. When the domain of the problem is large (e.g. traversal of a high-dimensional space), a perfect solution cannot be obtained, so approximations…

Biomolecules · Quantitative Biology 2019-06-26 Nathan Clement

Disordered proteins play essential roles in myriad cellular processes, yet their structural characterization remains a major challenge due to their dynamic and heterogeneous nature. We here present a community-driven initiative to address…

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