Parameterization and Application of the General Amber Force Field to Model Fluoro Substituted Furanose Moieties and Nucleosides

Research output: Contribution to journalArticlepeer-review

Abstract

Molecular mechanics force field calculations have historically shown significant limitations in modeling the energetic and conformational interconversions of highly substituted furanose rings. This is primarily due to the gauche effect that is not easily captured using pairwise energy potentials. In this study, we present a refinement to the set of torsional parameters in the General Amber Force Field (gaff ) used to calculate the potential energy of mono, di-, and gem-fluorinated nucleosides. The parameters were optimized to reproduce the pseudorotation phase angle and relative energies of a diverse set of mono-and difluoro substituted furanose ring systems using quantum mechanics umbrella sampling techniques available in the IpolQ engine in the Amber suite of programs. The parameters were developed to be internally consistent with the gaff force field and the TIP3P water model. The new set of angle and dihedral parameters and partial charges were validated by comparing the calculated phase angle probability to those obtained from experimental nuclear magnetic resonance experiments.

Original languageEnglish (US)
Article number2616
JournalMolecules
Volume27
Issue number9
DOIs
StatePublished - May 1 2022

Bibliographical note

Funding Information:
Funding: This research was supported by the National Institutes of Health R01 AI136445 and R01 AI143784. We are also grateful to the Minnesota NMR Center for providing NMR instrumentation and the Minnesota Supercomputing Institute for computational resources.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Amber
  • fluorinated
  • force field
  • furanose
  • molecular mechanics
  • NMR
  • nucleoside
  • sugar pucker

PubMed: MeSH publication types

  • Journal Article

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