Systematic comparison of atomistic force fields for the mechanical properties of double-stranded DNA

The response of double-stranded DNA to external mechanical stress plays a central role in its interactions with the protein machinery in the cell. Modern atomistic force fields have been shown to provide highly accurate predictions for the fine structural features of the duplex. In contrast, and des...

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Detalles Bibliográficos
Autores: Roldán Piñero, Carlos, Luengo Márquez, Juan, Assenza, Salvatore, Pérez Pérez, Rubén
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/711598
Acceso en línea:http://hdl.handle.net/10486/711598
https://dx.doi.org/10.1021/acs.jctc.3c01089
Access Level:acceso abierto
Palabra clave:Elasticity
Molecular Conformation
Molecular Dynamics Simulation
Nucleic Acid Conformation
Stress
Mechanical
Física
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spelling Systematic comparison of atomistic force fields for the mechanical properties of double-stranded DNARoldán Piñero, CarlosLuengo Márquez, JuanAssenza, SalvatorePérez Pérez, RubénElasticityMolecular ConformationMolecular Dynamics SimulationNucleic Acid ConformationStressMechanicalFísicaThe response of double-stranded DNA to external mechanical stress plays a central role in its interactions with the protein machinery in the cell. Modern atomistic force fields have been shown to provide highly accurate predictions for the fine structural features of the duplex. In contrast, and despite their pivotal function, less attention has been devoted to the accuracy of the prediction of the elastic parameters. Several reports have addressed the flexibility of double-stranded DNA via all-atom molecular dynamics, yet the collected information is insufficient to have a clear understanding of the relative performance of the various force fields. In this work, we fill this gap by performing a systematic study in which several systems, characterized by different sequence contexts, are simulated with the most popular force fields within the AMBER family, bcs1 and OL15, as well as with CHARMM36. Analysis of our results, together with their comparison with previous work focused on bsc0, allows us to unveil the differences in the predicted rigidity between the newest force fields and suggests a roadmap to test their performance against experiments. In the case of the stretch modulus, we reconcile these differences, showing that a single mapping between sequence-dependent conformation and elasticity via the crookedness parameter captures simultaneously the results of all force fields, supporting the key role of crookedness in the mechanical response of double-stranded DNAThe project that gave rise to these results received the support of a fellowship from the “la Caixa” Foundation (ID 100010434) and from the European Union’s Horizon research and innovation programme under Marie Skłodowska-Curie grant agreement no. 847648. The fellowship code is LCF/BQ/ PI20/11760019. S.A. acknowledges support from MCIN/AEI/ 10.13039/501100011033 and FSE + through a Ramón y Cajal Fellowship (ref. RYC2022-037744-I). We acknowledge support from the Ministerio de Ciencia e Innovación (MCIN) through the project PID2020-115864RB-I00 and the “María de Maeztu” Programme for Units of Excellence in R&D (grant no. CEX2018-000805-M)American Chemical SocietyDepartamento de Física Teórica de la Materia CondensadaFacultad de Ciencias20242024-02-27research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/711598https://dx.doi.org/10.1021/acs.jctc.3c01089reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 847648open accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7115982026-06-23T12:46:27Z
dc.title.none.fl_str_mv Systematic comparison of atomistic force fields for the mechanical properties of double-stranded DNA
title Systematic comparison of atomistic force fields for the mechanical properties of double-stranded DNA
spellingShingle Systematic comparison of atomistic force fields for the mechanical properties of double-stranded DNA
Roldán Piñero, Carlos
Elasticity
Molecular Conformation
Molecular Dynamics Simulation
Nucleic Acid Conformation
Stress
Mechanical
Física
title_short Systematic comparison of atomistic force fields for the mechanical properties of double-stranded DNA
title_full Systematic comparison of atomistic force fields for the mechanical properties of double-stranded DNA
title_fullStr Systematic comparison of atomistic force fields for the mechanical properties of double-stranded DNA
title_full_unstemmed Systematic comparison of atomistic force fields for the mechanical properties of double-stranded DNA
title_sort Systematic comparison of atomistic force fields for the mechanical properties of double-stranded DNA
dc.creator.none.fl_str_mv Roldán Piñero, Carlos
Luengo Márquez, Juan
Assenza, Salvatore
Pérez Pérez, Rubén
author Roldán Piñero, Carlos
author_facet Roldán Piñero, Carlos
Luengo Márquez, Juan
Assenza, Salvatore
Pérez Pérez, Rubén
author_role author
author2 Luengo Márquez, Juan
Assenza, Salvatore
Pérez Pérez, Rubén
author2_role author
author
author
dc.contributor.none.fl_str_mv Departamento de Física Teórica de la Materia Condensada
Facultad de Ciencias
dc.subject.none.fl_str_mv Elasticity
Molecular Conformation
Molecular Dynamics Simulation
Nucleic Acid Conformation
Stress
Mechanical
Física
topic Elasticity
Molecular Conformation
Molecular Dynamics Simulation
Nucleic Acid Conformation
Stress
Mechanical
Física
description The response of double-stranded DNA to external mechanical stress plays a central role in its interactions with the protein machinery in the cell. Modern atomistic force fields have been shown to provide highly accurate predictions for the fine structural features of the duplex. In contrast, and despite their pivotal function, less attention has been devoted to the accuracy of the prediction of the elastic parameters. Several reports have addressed the flexibility of double-stranded DNA via all-atom molecular dynamics, yet the collected information is insufficient to have a clear understanding of the relative performance of the various force fields. In this work, we fill this gap by performing a systematic study in which several systems, characterized by different sequence contexts, are simulated with the most popular force fields within the AMBER family, bcs1 and OL15, as well as with CHARMM36. Analysis of our results, together with their comparison with previous work focused on bsc0, allows us to unveil the differences in the predicted rigidity between the newest force fields and suggests a roadmap to test their performance against experiments. In the case of the stretch modulus, we reconcile these differences, showing that a single mapping between sequence-dependent conformation and elasticity via the crookedness parameter captures simultaneously the results of all force fields, supporting the key role of crookedness in the mechanical response of double-stranded DNA
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-02-27
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/711598
https://dx.doi.org/10.1021/acs.jctc.3c01089
url http://hdl.handle.net/10486/711598
https://dx.doi.org/10.1021/acs.jctc.3c01089
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 847648

dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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