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The rapid evolution of molecular dynamics (MD) methods, including machine-learned dynamics, has outpaced the development of standardized tools for method validation. Objective comparison between simulation approaches is often hindered by…

Molecular dynamics (MD) simulations play a crucial role in resolving the underlying conformational dynamics of molecular systems. However, their capability to correctly reproduce and predict dynamics in agreement with experiments is limited…

Chemical Physics · Physics 2025-05-19 Ivan Gilardoni , Valerio Piomponi , Thorben Fröhlking , Giovanni Bussi

Significant advances in biotechnology have allowed for simultaneous measurement of molecular data points across multiple genomic and transcriptomic levels from a single tumor/cancer sample. This has motivated systematic approaches to…

Biological processes, functions, and properties are intricately linked to the ensemble of protein conformations, rather than being solely determined by a single stable conformation. In this study, we have developed P2DFlow, a generative…

Biological Physics · Physics 2025-03-05 Yaowei Jin , Qi Huang , Ziyang Song , Mingyue Zheng , Dan Teng , Qian Shi

Many processes of scientific importance are characterized by time scales that extend far beyond the reach of standard simulation techniques. To circumvent this impediment a plethora of enhanced sampling methods has been developed. One…

Computational Physics · Physics 2018-12-05 Dan Mendels , Giovannimaria Piccini , Z. Faidon Brotzakis , Yi I. Yang , Michele Parrinello

The accurate screening of candidate drug ligands against target proteins through computational approaches is of prime interest to drug development efforts. Such virtual screening depends in part on methods to predict the binding affinity…

Machine Learning · Computer Science 2024-10-22 Ho-Joon Lee , Prashant S. Emani , Mark B. Gerstein

Characterizing structural and dynamic properties of proteins and large macromolecular assemblies is crucial to understand the molecular mechanisms underlying biological functions. In the field of Structural Biology, no single method…

Quantitative Methods · Quantitative Biology 2023-10-04 Samuel Hoff , Maximilian Zinke , Nadia Izadi-Pruneyre , Massimiliano Bonomi

Accurate prediction of protein-ligand binding affinities is an essential challenge in structure-based drug design. Despite recent advances in data-driven methods for affinity prediction, their accuracy is still limited, partially because…

Biomolecules · Quantitative Biology 2024-09-04 Yaosen Min , Ye Wei , Peizhuo Wang , Xiaoting Wang , Han Li , Nian Wu , Stefan Bauer , Shuxin Zheng , Yu Shi , Yingheng Wang , Ji Wu , Dan Zhao , Jianyang Zeng

Proteins and other macromolecules exist not in a single state but as dynamic ensembles of interconverting conformations, which are essential for catalysis, allosteric regulation, and molecular recognition. While AI-based structure…

Biomolecules · Quantitative Biology 2025-10-22 Stephanie A. Wankowicz , Massimiliano Bonomi

In a shotgun proteomics experiment, proteins are the most biologically meaningful output. The success of proteomics studies depends on the ability to accurately and efficiently identify proteins. Many methods have been proposed to…

Quantitative Methods · Quantitative Biology 2012-11-30 Chao Yang , Zengyou He , Weichuan Yu

All-atom molecular dynamics (MD) computer simulations are a valuable tool for characterizing the conformational ensembles of intrinsically disordered proteins (IDPs). IDP conformational ensembles are highly heterogeneous and contain…

Chemical Physics · Physics 2025-05-06 Jaya Krishna Koneru , Korey M. Reid , Paul Robustelli

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

Infrequent Metadynamics is a popular method to obtain the rates of long timescale processes from accelerated simulations. The inference procedure is based on rescaling the first-passage times of Metadynamics trajectories using a…

Chemical Physics · Physics 2025-03-04 Ofir Blumer , Shlomi Reuveni , Barak Hirshberg

The biological properties of proteins are uniquely determined by their structure and dynamics. A protein in solution populates a structural ensemble of metastable configurations around the global fold. From overall rotation to local…

Biological Physics · Physics 2015-12-09 J. Copperman , M. G. Guenza

Deep learning is catalyzing a scientific revolution fueled by big data, accessible toolkits, and powerful computational resources, impacting many fields including protein structural modeling. Protein structural modeling, such as predicting…

Biomolecules · Quantitative Biology 2020-07-17 Wenhao Gao , Sai Pooja Mahajan , Jeremias Sulam , Jeffrey J. Gray

As a nonlocal extension of continuum mechanics, peridynamics has been widely and effectively applied in different fields where discontinuities in the field variables arise from an initially continuous body. An important component of the…

Numerical Analysis · Mathematics 2021-09-22 Xiao Xu , Marta D'Elia , John T. Foster

The problem of inferring proteins from complex peptide cocktails (digestion products of biological samples) in shotgun proteomic workflow sets extreme demands on computational resources in respect of the required very high processing…

Computational Engineering, Finance, and Science · Computer Science 2014-12-30 S. M. Vidanagamachchi , S. D. Dewasurendra , R. G. Ragel , M. Niranjan

Protein structure prediction is a challenging and unsolved problem in computer science. Proteins are the sequence of amino acids connected together by single peptide bond. The combinations of the twenty primary amino acids are the…

Computational Engineering, Finance, and Science · Computer Science 2015-10-12 Mahmood A. Rashid , Firas Khatib , Abdul Sattar

Composed of amino acid chains that influence how they fold and thus dictating their function and features, proteins are a class of macromolecules that play a central role in major biological processes and are required for the structure,…

Quantitative Methods · Quantitative Biology 2022-07-15 Aaron Wang

This review article provides an overview of structurally oriented experimental datasets that can be used to benchmark protein force fields, focusing on data generated by nuclear magnetic resonance (NMR) spectroscopy and room temperature…