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Predicting the change in binding free energy ($\Delta \Delta G$) is crucial for understanding and modulating protein-protein interactions, which are critical in drug design. Due to the scarcity of experimental $\Delta \Delta G$ data,…

Computational Engineering, Finance, and Science · Computer Science 2024-10-15 Xiaoran Jiao , Weian Mao , Wengong Jin , Peiyuan Yang , Hao Chen , Chunhua Shen

Predicting changes in binding free energy ($\Delta\Delta G$) is a vital task in protein engineering and protein-protein interaction (PPI) engineering for drug discovery. Previous works have observed a high correlation between $\Delta\Delta…

Machine Learning · Computer Science 2025-08-15 Patrick Soga , Zhenyu Lei , Yinhan He , Camille Bilodeau , Jundong Li

A protein's function depends critically on its conformational ensemble, a collection of energy weighted structures whose balance depends on temperature and environment. Though recent deep learning (DL) methods have substantially advanced…

Biomolecules · Quantitative Biology 2026-01-09 Myeongsang Lee , Lauren L. Porter

Directed evolution plays an indispensable role in protein engineering that revises existing protein sequences to attain new or enhanced functions. Accurately predicting the effects of protein variants necessitates an in-depth understanding…

Quantitative Methods · Quantitative Biology 2023-06-09 Yang Tan , Bingxin Zhou , Yuanhong Jiang , Yu Guang Wang , Liang Hong

Many aspects of the study of protein folding and dynamics have been affected by the recent advances in machine learning. Methods for the prediction of protein structures from their sequences are now heavily based on machine learning tools.…

Biological Physics · Physics 2019-11-25 Frank Noé , Gianni De Fabritiis , Cecilia Clementi

Inverse folding models have proven to be highly effective zero-shot predictors of protein stability. Despite this success, the link between the amino acid preferences of an inverse folding model and the free-energy considerations underlying…

Many crucial biological processes rely on networks of protein-protein interactions. Predicting the effect of amino acid mutations on protein-protein binding is vital in protein engineering and therapeutic discovery. However, the scarcity of…

Biomolecules · Quantitative Biology 2023-11-01 Shiwei Liu , Tian Zhu , Milong Ren , Chungong Yu , Dongbo Bu , Haicang Zhang

Accurate prediction and optimization of protein-protein binding affinity is crucial for therapeutic antibody development. Although machine learning-based prediction methods $\Delta\Delta G$ are suitable for large-scale mutant screening,…

Biomolecules · Quantitative Biology 2024-09-19 Kairi Furui , Masahito Ohue

Despite recent advances in protein-ligand structure prediction, deep learning methods remain limited in their ability to accurately predict binding affinities, particularly for novel protein targets dissimilar from the training set. In…

Quantitative Methods · Quantitative Biology 2025-12-04 Michael Brocidiacono , James Wellnitz , Konstantin I. Popov , Alexander Tropsha

Designing protein sequences with optimal energetic stability is a key challenge in protein inverse folding, as current deep learning methods are primarily trained by maximizing sequence recovery rates, often neglecting the energy of the…

Machine Learning · Computer Science 2025-06-12 Dingyi Rong , Haotian Lu , Wenzhuo Zheng , Fan Zhang , Shuangjia Zheng , Ning Liu

A basic question of protein structural studies is to which extent mutations affect the stability. This question may be addressed starting from sequence and/or from structure. In proteomics and genomics studies prediction of protein…

Biomolecules · Quantitative Biology 2007-06-13 Emidio Capriotti , Piero Fariselli , Ivan Rossi , Rita Casadio

Modeling the interaction between proteins and ligands and accurately predicting their binding structures is a critical yet challenging task in drug discovery. Recent advancements in deep learning have shown promise in addressing this…

Machine Learning · Computer Science 2024-01-10 Qizhi Pei , Kaiyuan Gao , Lijun Wu , Jinhua Zhu , Yingce Xia , Shufang Xie , Tao Qin , Kun He , Tie-Yan Liu , Rui Yan

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…

Understanding the relationship between protein sequence, function, and stability is a fundamental problem in biology. While high-throughput methods have produced large numbers of sequence-function pairs, functional assays do not distinguish…

Biomolecules · Quantitative Biology 2018-12-03 Jakub Otwinowski

The prediction of protein stability changes following single-point mutations plays a pivotal role in computational biology, particularly in areas like drug discovery, enzyme reengineering, and genetic disease analysis. Although…

Quantitative Methods · Quantitative Biology 2025-05-01 Ivan Rossi , Guido Barducci , Tiziana Sanavia , Paola Turina , Emidio Capriotti , Piero Fariselli

Protein structure prediction is pivotal for understanding the structure-function relationship of proteins, advancing biological research, and facilitating pharmaceutical development and experimental design. While deep learning methods and…

Machine Learning · Computer Science 2024-12-30 Kaihui Cheng , Ce Liu , Qingkun Su , Jun Wang , Liwei Zhang , Yining Tang , Yao Yao , Siyu Zhu , Yuan Qi

Developing accurate and efficient coarse-grained representations of proteins is crucial for understanding their folding, function, and interactions over extended timescales. Our methodology involves simulating proteins with molecular…

Biomolecules · Quantitative Biology 2023-10-11 Carles Navarro , Maciej Majewski , Gianni de Fabritiis

MOTIVATION: Proteins fold into complex structures that are crucial for their biological functions. Experimental determination of protein structures is costly and therefore limited to a small fraction of all known proteins. Hence, different…

Biomolecules · Quantitative Biology 2018-04-18 David Menéndez Hurtado , Karolis Uziela , Arne Elofsson

Motivation: Site directed mutagenesis is widely used to understand the structure and function of biomolecules. Computational prediction of protein mutation impacts offers a fast, economical and potentially accurate alternative to laboratory…

Quantitative Methods · Quantitative Biology 2017-04-03 Zixuan Cang , Guo-Wei Wei

Most widely used ligand docking methods assume a rigid protein structure. This leads to problems when the structure of the target protein deforms upon ligand binding. In particular, the ligand's true binding pose is often scored very…

Biomolecules · Quantitative Biology 2023-03-22 Patricia Suriana , Joseph M. Paggi , Ron O. Dror
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