+ Most Popular
Cunninghamia lanceolata plantations in China
Mammalian lairs in paleo ecological studies and palynology
Studies on technological possibilities in utilization of anhydrous milk fat for production of recombined butter-like products
Should right-sided fibroelastomas be operated upon?
Large esophageal lipoma
Apoptosis in the mammalian thymus during normal histogenesis and under various in vitro and in vivo experimental conditions
Poissons characoides nouveaux ou non signales de l'Ilha do Bananal, Bresil
Desensitizing efficacy of Colgate Sensitive Maximum Strength and Fresh Mint Sensodyne dentifrices
Administration of fluid by subcutaneous infusion: revival of a forgotten method
Tundra mosquito control - an impossible dream?
Schizophrenia for primary care providers: how to contribute to the care of a vulnerable patient population
Geochemical pattern analysis; method of describing the Southeastern limestone regional aquifer system
Incidence of low birth weights in a hospital of Mexico City
Graded management intensity of grassland systems for enhancing floristic diversity
Microbiology and biochemistry of cheese and fermented milk
The ember tetra: a new pygmy characid tetra from the Rio das Mortes, Brazil, Hyphessobrycon amandae sp. n. (Pisces, Characoidei)
Risk factors of contrast-induced nephropathy in patients after coronary artery intervention
Renovation of onsite domestic wastewater in a poorly drained soil
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Systolic blood pressure in a population of infants in the first year of life: the Brompton study
Haematological studies in rats fed with metanil yellow
Studies on pasteurellosis. I. A new species of Pasteurella encountered in chronic fowl cholera
Dormancy breaking and germination of Acacia salicina Lindl. seeds
therapy of lupus nephritis. a two-year prospective study

Improved Modeling of Halogenated Ligand-Protein Interactions Using the Drude Polarizable and CHARMM Additive Empirical Force Fields

Improved Modeling of Halogenated Ligand-Protein Interactions Using the Drude Polarizable and CHARMM Additive Empirical Force Fields

Journal of Chemical Information and Modeling 59(1): 215-228

ISSN/ISBN: 1549-9596

PMID: 30418023

DOI: 10.1021/acs.jcim.8b00616

Halogenated ligands can participate in nonbonding interactions with proteins via halogen bond (XB) or halogen-hydrogen bond donor (X-HBD) interactions. In the context of molecular dynamics (MD) simulations, the accuracy of the simulations depends strongly on the force field (FF) used. To ensure good reproduction of XB and X-HBD interactions with proteins, we optimized the previously developed additive CHARMM36/CHARMM General force field (CGenFF) and Drude polarizable force field by including atom pair-specific Lennard-Jones parameters for aromatic halogen-protein interactions. The optimization targeted quantum mechanical interaction energy surfaces with the developed parameters then examined for their ability to reproduce experimental halogen-containing ligand-protein interactions in MD simulations. The calculated halogenated ligand interaction geometries were in good overall agreement with the experimental crystal data for both the polarizable and additive FFs, showing that these models can accurately treat both XB and X-HBD interactions. Analysis of the ligand-protein interactions shows significant contributions of polarizability to binding occurring in the Drude FF, with self-polarization energy making both favorable and unfavorable contributions to binding. Further analysis of the dipole moments from aqueous solution to protein indicates the polarizable FF accounts for subtle changes of the environment of the ligands that can impact binding. The present work demonstrates the utility of the updated additive CHARMM36/CGenFF and polarizable Drude FFs for the study of halogenated ligand-protein interactions in computer-aided drug design.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 065813919

Download citation: RISBibTeXText

Related references

A comparative Kirkwood-Buff study of aqueous methanol solutions modeled by the CHARMM additive and Drude polarizable force fields. Journal of Physical Chemistry. B 117(36): 10572-10580, 2013

Kirkwood-Buff analysis of aqueous N-methylacetamide and acetamide solutions modeled by the CHARMM additive and Drude polarizable force fields. Journal of Chemical Physics 139(8): 084509, 2013

Improved Modeling of Cation-π and Anion-Ring Interactions Using the Drude Polarizable Empirical Force Field for Proteins. Journal of Computational Chemistry 41(5): 439-448, 2020

FFParam: Standalone package for CHARMM additive and Drude polarizable force field parametrization of small molecules. Journal of Computational Chemistry 41(9): 958-970, 2020

CHARMM-GUi Drude prepper for molecular dynamics simulation using the classical Drude polarizable force field. Journal of Computational Chemistry 43(5): 359-375, 2022

CHARMM additive and polarizable force fields for biophysics and computer-aided drug design. Biochimica et Biophysica Acta 1850(5): 861-871, 2015

Additive and Classical Drude Polarizable Force Fields for Linear and Cyclic Ethers. Journal of Chemical Theory and Computation 3(3): 1120-1133, 2007

CHARMM Drude Polarizable Force Field for Aldopentofuranoses and Methyl-aldopentofuranosides. Journal of Physical Chemistry. B 119(25): 7846-7859, 2015

Competition among Li(+), Na(+), K(+), and Rb(+) monovalent ions for DNA in molecular dynamics simulations using the additive CHARMM36 and Drude polarizable force fields. Journal of Physical Chemistry. B 119(12): 4428-4440, 2015

Assessment of the DNA partial specific volume and hydration layer properties from CHARMM Drude polarizable and additive MD simulations. Physical Chemistry Chemical Physics: Pccp 23(17): 10524-10535, 2021

CHARMM Drude Polarizable Force Field for Glycosidic Linkages Involving Pyranoses and Furanoses. Journal of Chemical Theory and Computation 14(6): 3132-3143, 2018

Extension of the CHARMM Classical Drude Polarizable Force Field to N- and O-Linked Glycopeptides and Glycoproteins. Journal of Physical Chemistry. B 2022, 2022

Polarizability rescaling and atom-based Thole scaling in the CHARMM Drude polarizable force field for ethers. Journal of Molecular Modeling 16(3): 567-576, 2010

Folding free energy landscapes of β-sheets with non-polarizable and polarizable CHARMM force fields. Journal of Chemical Physics 149(7): 072317, 2018

Parametrization of halogen bonds in the CHARMM general force field: Improved treatment of ligand-protein interactions. Bioorganic and Medicinal Chemistry 24(20): 4812-4825, 2016