A Density Functional Theory and Molecular Dynamics Study of Antifolate Molecules under Physiological Conditions

Abstract

The current study mainly focuses on the investigation of the antioxidant property and the dynamic behaviour of four antifolate molecules and comparision with folic acid. DFT (wB97X/6‐31+G(d)) level of theory was employed to calculate the N‐H bond dissociation energy (BDE) of the heterocyclic amino group and vertical ionization potential (IPv) of the molecules in water. The results reveal that studied antifolate molecules are very similar to folate with respect to the antioxidant property. Spin density plots and second‐order perturbation energies (E2) were calculated to show the stability of the hydrogen abstracted radicals and radical cations resulting from the folate and antifolate molecules. In addition, MD simulations were carried out to investigate conformational stability of molecules. Various properties like hydrogen bond, RMSD, SASA, cluster structure analysis were explored to study the conformational behaviour of the molecules. The results obtained from MD simulations are again very similar for folate and antifolates under investigation. The results obtained from the current study would help to understand the interaction of the antifolate molecules with folic acid receptors and also to design new molecules with better activity as drugs.

Evaluation of the electronic density at critical points of hydrogen bonds: PM7 a good alternative to ab‐initio methods

“…Finally, for GT2 there are hydrogen bonds: CHÁÁÁO and NHÁÁÁN. The findings reported by Choudhury et al[66] support this information.…”

“…Finally, for GT2 there are hydrogen bonds: $$$ CH\cdots \mathbf{O} $$$ and $$$ NH\cdots \mathbf{N} $$$. The findings reported by Choudhury et al [66] support this information.…”

“… Note : In the case of KS‐DFT, the methodology used by Choudhury et al [66] is: $$$ \omega $$$B97XD/6‐311++G(2d,2p). All values in a.u. …”

“…In α-helices one type of hydrogen bonding interaction found is between the N H group at position i and the C O group at position i + 4 (see Figure 7). This bonding Note: In the case of KS-DFT, the methodology used by Choudhury et al [66] is: ωB97XD/6-311++G(2d,2p). All values in a.u.…”

Investigating Hydrogen Bonding Interactions in Aniline‐Acetone Binary Mixture through Molecular Dynamics Simulations

“…Aniline has α values of 0.26 and β values of 0.50, [31] while acetone has α values of 0.0 and and β value 0.50 [32] . Aniline and acetone, with an amine group (NH 2 ) and carbonyl group (C=O) respectively are capable of forming (a) NH−O and (b) NH−N strong HBs within aniline and between aniline and acetone which serve as a prototype for studying these types of HBs in biomolecular systems such as DNA, RNA, and other biological interactions [33–35] . A detailed computational study of these hydrogen bond interactions has not been done yet.…”