Conformational Analysis of Neutral and Ionic Arginine Forms Using DFT Methods

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.