Balancing Group 1 Monoatomic Ion-Polar Compound Interactions in the Polarizable Drude Force Field: Application in Protein and Nucleic Acid Systems

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dc.contributor.authorNan, Yilingen
dc.contributor.authorBaral, Prabinen
dc.contributor.authorOrr, Asuka A.en
dc.contributor.authorMichel, Haley M.en
dc.contributor.authorLemkul, Justin A.en
dc.contributor.authorMackerell, Alexander D.en
dc.date.accessioned2025-01-08T18:38:33Zen
dc.date.available2025-01-08T18:38:33Zen
dc.date.issued2024-12-03en
dc.description.abstractAn accurate force field (FF) is the foundation of reliable results from molecular dynamics (MD) simulations. In our recently published work, we developed a protocol to generate atom pair-specific Lennard-Jones (known as NBFIX in CHARMM) and through-space Thole dipole screening (NBTHOLE) parameters in the context of the Drude polarizable FF based on readily accessible quantum mechanical (QM) data to fit condensed phase experimental thermodynamic benchmarks, including the osmotic pressure, diffusion coefficient, ionic conductivity, and solvation free energy, when available. In the present work, the developed protocol is applied to generate NBFIX and NBTHOLE parameters for interactions between monatomic ions (specifically Li+, Na+, K+, Rb+, Cs+, and Cl-) and common functional groups found in proteins and nucleic acids. The parameters generated for each ion-functional group pair were then applied to the corresponding functional groups within proteins or nucleic acids followed by MD simulations to analyze the distribution of ions around these biomolecules. The modified FF successfully addresses the issue of overbinding observed in a previous iteration of the Drude FF. Quantitatively, the model accurately reproduces the effective charge of proteins and demonstrates a level of charge neutralization for a double-helix B-DNA in good agreement with the counterion condensation theory. Additionally, simulations involving ion competition correlate well with experimental results, following the trend Li+ > Na+ ≈ K+ > Rb+. These results validate the refined model for group 1 ion-biomolecule interactions that will facilitate the application of the polarizable Drude FF in systems in which group 1 ions play an important role.en
dc.description.versionAccepted versionen
dc.format.extentPages 12078-12091en
dc.format.extent14 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1021/acs.jpcb.4c06354en
dc.identifier.eissn1520-5207en
dc.identifier.issn1520-6106en
dc.identifier.issue49en
dc.identifier.orcidLemkul, Justin [0000-0001-6661-8653]en
dc.identifier.pmid39625472en
dc.identifier.urihttps://hdl.handle.net/10919/123966en
dc.identifier.volume128en
dc.language.isoenen
dc.publisherAmerican Chemical Societyen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/39625472en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subject.meshMolecular Dynamics Simulationen
dc.subject.meshProteinsen
dc.subject.meshNucleic Acidsen
dc.subject.meshIonsen
dc.subject.meshThermodynamicsen
dc.subject.meshQuantum Theoryen
dc.titleBalancing Group 1 Monoatomic Ion-Polar Compound Interactions in the Polarizable Drude Force Field: Application in Protein and Nucleic Acid Systemsen
dc.title.serialJournal of Physical Chemistry Ben
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
pubs.organisational-groupVirginia Techen
pubs.organisational-groupVirginia Tech/Agriculture & Life Sciencesen
pubs.organisational-groupVirginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-groupVirginia Tech/All T&R Facultyen
pubs.organisational-groupVirginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen

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