Conformational Analysis and Electronic Structure of Folic Acid: A Theoretical Study

Igor Novak, Fatemeh Abyar

Research output: Contribution to journalArticle

Abstract

Folic acid decomposes when exposed to UV light so understanding the effect of light on this biomolecule is very important. In this study, sixty conformers of folic acid were investigated by DFT calculations. Six most stable conformers were selected for study of their electronic structure and photoelectron spectra. The photoelectron spectra were simulated by two high level ab initio computational methods. Two methods used to obtain valence ionization energies were general-R symmetry adapted cluster-configuration interaction (general-R-SAC-CI) method and outer-valence Green's function (OVGF). The SAC-CI computations were performed with two different basis sets: D95 (df,pd) and 6-311G(d,p). Because of the size of the folic acid molecule, OVGF calculations were only performed with 6-311G(d,p) basis set. The calculated photoelectron spectrum of folic acid was obtained by superposition of weighted photoelectron spectra of individual conformers. Natural Bonding Orbitals (NBO) calculations were performed for the assignment of ionization bands of each conformer. It is shown that ionization occurs mostly from the orbitals localized on p-aminobenzoyl moiety in folic acid. Koopmans’ approximation is only applicable for describing the five lowest energy orbital ionizations (photoelectron bands). The in-situ molecular structures of two bio-active conformers were extracted from X-ray diffraction data obtained for folic acid bound to folate receptor protein. The unmodified molecular structures were then used for calculating ionization energies. We discuss the consequences for ligand-receptor binding of switching from the most stable conformation to bioactive conformation in FA.
LanguageEnglish
Pages819-825
Number of pages7
JournalJournal of Molecular Liquids
Volume276
Publication statusPublished - 2019

Fingerprint

folic acid
Folic Acid
Electronic structure
Photoelectrons
electronic structure
photoelectrons
Acids
ionization
Ionization
Ionization potential
valence
Green's function
orbitals
Molecular structure
Conformations
molecular structure
Green's functions
Orbital calculations
Biomolecules
Computational methods

Grant Number

  • OPA4068

Cite this

@article{96ad0e49bb7248509b5b0129f36e3ac4,
title = "Conformational Analysis and Electronic Structure of Folic Acid: A Theoretical Study",
abstract = "Folic acid decomposes when exposed to UV light so understanding the effect of light on this biomolecule is very important. In this study, sixty conformers of folic acid were investigated by DFT calculations. Six most stable conformers were selected for study of their electronic structure and photoelectron spectra. The photoelectron spectra were simulated by two high level ab initio computational methods. Two methods used to obtain valence ionization energies were general-R symmetry adapted cluster-configuration interaction (general-R-SAC-CI) method and outer-valence Green's function (OVGF). The SAC-CI computations were performed with two different basis sets: D95 (df,pd) and 6-311G(d,p). Because of the size of the folic acid molecule, OVGF calculations were only performed with 6-311G(d,p) basis set. The calculated photoelectron spectrum of folic acid was obtained by superposition of weighted photoelectron spectra of individual conformers. Natural Bonding Orbitals (NBO) calculations were performed for the assignment of ionization bands of each conformer. It is shown that ionization occurs mostly from the orbitals localized on p-aminobenzoyl moiety in folic acid. Koopmans’ approximation is only applicable for describing the five lowest energy orbital ionizations (photoelectron bands). The in-situ molecular structures of two bio-active conformers were extracted from X-ray diffraction data obtained for folic acid bound to folate receptor protein. The unmodified molecular structures were then used for calculating ionization energies. We discuss the consequences for ligand-receptor binding of switching from the most stable conformation to bioactive conformation in FA.",
author = "Igor Novak and Fatemeh Abyar",
year = "2019",
language = "English",
volume = "276",
pages = "819--825",
journal = "Journal of Molecular Liquids",
issn = "0167-7322",
publisher = "Elsevier",

}

Conformational Analysis and Electronic Structure of Folic Acid: A Theoretical Study. / Novak, Igor; Abyar, Fatemeh.

In: Journal of Molecular Liquids, Vol. 276, 2019, p. 819-825.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Conformational Analysis and Electronic Structure of Folic Acid: A Theoretical Study

AU - Novak, Igor

AU - Abyar, Fatemeh

PY - 2019

Y1 - 2019

N2 - Folic acid decomposes when exposed to UV light so understanding the effect of light on this biomolecule is very important. In this study, sixty conformers of folic acid were investigated by DFT calculations. Six most stable conformers were selected for study of their electronic structure and photoelectron spectra. The photoelectron spectra were simulated by two high level ab initio computational methods. Two methods used to obtain valence ionization energies were general-R symmetry adapted cluster-configuration interaction (general-R-SAC-CI) method and outer-valence Green's function (OVGF). The SAC-CI computations were performed with two different basis sets: D95 (df,pd) and 6-311G(d,p). Because of the size of the folic acid molecule, OVGF calculations were only performed with 6-311G(d,p) basis set. The calculated photoelectron spectrum of folic acid was obtained by superposition of weighted photoelectron spectra of individual conformers. Natural Bonding Orbitals (NBO) calculations were performed for the assignment of ionization bands of each conformer. It is shown that ionization occurs mostly from the orbitals localized on p-aminobenzoyl moiety in folic acid. Koopmans’ approximation is only applicable for describing the five lowest energy orbital ionizations (photoelectron bands). The in-situ molecular structures of two bio-active conformers were extracted from X-ray diffraction data obtained for folic acid bound to folate receptor protein. The unmodified molecular structures were then used for calculating ionization energies. We discuss the consequences for ligand-receptor binding of switching from the most stable conformation to bioactive conformation in FA.

AB - Folic acid decomposes when exposed to UV light so understanding the effect of light on this biomolecule is very important. In this study, sixty conformers of folic acid were investigated by DFT calculations. Six most stable conformers were selected for study of their electronic structure and photoelectron spectra. The photoelectron spectra were simulated by two high level ab initio computational methods. Two methods used to obtain valence ionization energies were general-R symmetry adapted cluster-configuration interaction (general-R-SAC-CI) method and outer-valence Green's function (OVGF). The SAC-CI computations were performed with two different basis sets: D95 (df,pd) and 6-311G(d,p). Because of the size of the folic acid molecule, OVGF calculations were only performed with 6-311G(d,p) basis set. The calculated photoelectron spectrum of folic acid was obtained by superposition of weighted photoelectron spectra of individual conformers. Natural Bonding Orbitals (NBO) calculations were performed for the assignment of ionization bands of each conformer. It is shown that ionization occurs mostly from the orbitals localized on p-aminobenzoyl moiety in folic acid. Koopmans’ approximation is only applicable for describing the five lowest energy orbital ionizations (photoelectron bands). The in-situ molecular structures of two bio-active conformers were extracted from X-ray diffraction data obtained for folic acid bound to folate receptor protein. The unmodified molecular structures were then used for calculating ionization energies. We discuss the consequences for ligand-receptor binding of switching from the most stable conformation to bioactive conformation in FA.

M3 - Article

VL - 276

SP - 819

EP - 825

JO - Journal of Molecular Liquids

T2 - Journal of Molecular Liquids

JF - Journal of Molecular Liquids

SN - 0167-7322

ER -