# Conformational Analysis of Neutral and Ionic Arginine Forms Using DFT Methods

## TL;DR

This study uses computational methods to analyze the different conformations of arginine in both neutral and ionic forms, revealing new stable structures that could impact protein function.

## Contribution

The study reports previously unreported conformations of cationic arginine and identifies new stable forms through DFT calculations.

## Key findings

- New stable conformers of arginine were identified in both vacuum and aqueous environments.
- Some zwitterionic and cationic forms of arginine were found to be unstable and convert to other forms via hydrogen transfer.
- The structural integrity of the most stable conformers was verified using MP2 reoptimization and frequency analysis.

## Abstract

Arginine (Arg) is
an essential amino acid with a side chain that
contains a positively charged group. Arg plays a pivotal role in maintaining
the overall charge balance of a protein due to the presence of the
guanidino group as its side chain. Consequently, Arg has the capacity
to influence various functional characteristics of proteins, encompassing
aspects such as folding, solubility, and aggregation. Moreover, the
ionic forms of this amino acid can be deemed to be critical determinants
in the formation of molecular interactions between proteins and organic
compounds. The versatile properties of Arg encompass a broad spectrum
of effects, ranging from cellular-level biochemical events to the
overall biological functions of the organism. Intriguingly, our knowledge
remains incomplete regarding the exhaustive characterization of all
potential forms of Arg. This gap in systematic examination within
the literature underscores the pressing need for further research
in order to comprehensively obtain a clear understanding of the role
of Arg within biological systems. The current study aims to investigate
all possible conformers of various Arg forms using density functional
theory (DFT) in both aqueous and gas phases. First, all possible initial
structures for each ionic and neutral Arg form were obtained by conformational
analysis using Spartan’16 software. Second, all obtained structures
were optimized by DFT using ωB97XD and B3LYP functionals in
combination with the 6-311++G­(d,p) basis set as implemented in Gaussian09
software. The two most stable configurations from the optimized geometries
were subjected to a reoptimization process using the MP2/6-311++G­(d,p)
method to verify their structural integrity. The minimum nature of
the optimized structures was verified by frequency analysis performed
at both calculation levels. We compared the optimization results of
the isoelectronic species in terms of their structures and electronic
energies. To the best of our knowledge, these conformations of cationic
Arg have not been previously reported in the literature. Also, our
calculations have shown that some of the zwitterionic and cationic
forms are not stable and are converted to other stable forms through
hydrogen transfer from the guanidine group to the α-amino group
after optimization by both DFT functionals. According to the results
of this study, new stable conformers for Arg were identified in both
vacuum and aqueous environments through the applied DFT functionals.