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The formation and proliferation of protein aggregates play a central role in a number of devastating neuro-degenerative diseases. Many experimental studies indicate that the ability of existing aggregates to replicate is a key property in…

Biological Physics · Physics 2020-08-25 Georg Meisl , Alexander J Dear , Thomas CT Michaels , Tuomas PJ Knowles

The elastic network (EN) is a prime model that describes the long-time dynamics of biomolecules. However, the use of harmonic potentials renders this model insufficient for studying large conformational changes of proteins (e.g. stretching…

Biological Physics · Physics 2018-11-06 A. B. Poma , M. S. Li , P. E. Theodorakis

Identification of protein-protein interactions (PPIs) helps derive cellular mechanistic understanding, particularly in the context of complex conditions such as neurodegenerative disorders, metabolic syndromes, and cancer. Large Language…

Machine Learning · Computer Science 2025-08-18 Sanket Jantre , Tianle Wang , Gilchan Park , Kriti Chopra , Nicholas Jeon , Xiaoning Qian , Nathan M. Urban , Byung-Jun Yoon

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

Elastic network models (ENMs) are valuable and efficient tools for characterizing the collective internal dynamics of proteins based on the knowledge of their native structures. The increasing evidence that the biological functionality of…

Biomolecules · Quantitative Biology 2015-09-01 Giovanni Pinamonti , Sandro Bottaro , Cristian Micheletti , Giovanni Bussi

The primary objective of flexibility analysis is to identify and define the feasibility region, which represents the range of operational conditions (e.g., variations in process parameters) that ensure safe, reliable, and feasible process…

Optimization and Control · Mathematics 2025-03-11 Segei Kucherenko , Nilay Shah , Oleksiy Klymenko

Protein-ligand binding is essential to almost all life processes. The understanding of protein-ligand interactions is fundamentally important to rational drug design and protein design. Based on large scale data sets, we show that protein…

Biomolecules · Quantitative Biology 2017-04-21 Duc Duy Nguyen , Tian Xiao , Menglun Wang , Guo-Wei Wei

How do living cells achieve sufficient abundances of functional protein complexes while minimizing promiscuous non-functional interactions? Here we study this problem using a first-principle model of the cell whose phenotypic traits are…

Biomolecules · Quantitative Biology 2011-01-04 Muyoung Heo , Sergei Maslov , Eugene I. Shakhnovich

We have studied the mobility of the folding catalyst, protein disulphide-isomerase (PDI), by molecular dynamics and by a rapid approach based on flexibility. We analysed our simulations using measures of backbone movement, relative…

Evolutionally conserved quantity that specifies folding nuclei is pursued by a case study for a small protein (PDB code: 1ten). First it is demonstrated that the sequences of amino acids at folding nuclei are not conserved. Then 3D…

Biological Physics · Physics 2007-05-23 S. Nakamura , O. Narikiyo

Molecular docking that predicts the bound structures of small molecules (ligands) to their protein targets, plays a vital role in drug discovery. However, existing docking methods often face limitations: they either overlook crucial…

Quantitative Methods · Quantitative Biology 2025-02-24 Zizhuo Zhang , Lijun Wu , Kaiyuan Gao , Jiangchao Yao , Tao Qin , Bo Han

Protein function prediction is a crucial task in bioinformatics, with significant implications for understanding biological processes and disease mechanisms. While the relationship between sequence and function has been extensively…

Quantitative Methods · Quantitative Biology 2024-09-04 Shania Mitra , Lei Huang , Manolis Kellis

Protein interactions are important in a broad range of biological processes. Traditionally, computational methods have been developed to automatically predict protein interface from hand-crafted features. Recent approaches employ deep…

Machine Learning · Computer Science 2020-07-21 Yi Liu , Hao Yuan , Lei Cai , Shuiwang Ji

Phi-values are experimental measures of the effects of mutations on the folding kinetics of a protein. A central question is which structural information Phi-values contain about the transition state of folding. Traditionally, a Phi-value…

Biomolecules · Quantitative Biology 2007-05-23 Thomas R. Weikl , Ken A. Dill

We developed a multiscale approach (MultiSCAAL) that integrates the potential of mean force (PMF) obtained from all-atomistic molecular dynamics simulations with a knowledge-based energy function for coarse-grained molecular simulations in…

Biological Physics · Physics 2010-05-10 Antonios Samiotakis , Dirar Homouz , Margaret S. Cheung

The prediction of protein interactions (CPIs) is crucial for the in-silico screening step in drug discovery. Recently, many end-to-end representation learning methods using deep neural networks have achieved significantly better performance…

Quantitative Methods · Quantitative Biology 2020-11-30 Jingtao Wang , Xi Li , Hua Zhang

Recent advances in geometric deep learning and generative modeling have enabled the design of novel proteins with a wide range of desired properties. However, current state-of-the-art approaches are typically restricted to generating…

Biomolecules · Quantitative Biology 2025-08-26 Vsevolod Viliuga , Leif Seute , Nicolas Wolf , Simon Wagner , Arne Elofsson , Jan Stühmer , Frauke Gräter

Motivation: Drug discovery demands rapid quantification of compound-protein interaction (CPI). However, there is a lack of methods that can predict compound-protein affinity from sequences alone with high applicability, accuracy, and…

Biomolecules · Quantitative Biology 2020-12-17 Mostafa Karimi , Di Wu , Zhangyang Wang , Yang Shen

Shortly after the determination of the first protein x-ray crystal structures, researchers analyzed their cores and reported packing fractions $\phi \approx 0.75$, a value that is similar to close packing equal-sized spheres. A limitation…

Biomolecules · Quantitative Biology 2016-04-06 Jennifer C. Gaines , W. Wendell Smith , Lynne Regan , Corey S. O'Hern

Resolving the structural variability of proteins is often key to understanding the structure-function relationship of those macromolecular machines. Single particle analysis using Cryogenic electron microscopy (CryoEM), combined with…

Quantitative Methods · Quantitative Biology 2022-11-22 Muyuan Chen , Bogdan Toader , Roy Lederman
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