title: Exploring chemical reaction mechanisms through harmonic Fourier beads path optimization.
abstract: Here, we apply the harmonic Fourier beads (HFB) path optimization method to study chemical reactions involving covalent bond breaking and forming on quantum mechanical (QM) and hybrid QM∕molecular mechanical (QM∕MM) potential energy surfaces. To improve efficiency of the path optimization on such computationally demanding potentials, we combined HFB with conjugate gradient (CG) optimization. The combined CG-HFB method was used to study two biologically relevant reactions, namely, L- to D-alanine amino acid inversion and alcohol acylation by amides. The optimized paths revealed several unexpected reaction steps in the gas phase. For example, on the B3LYP∕6-31G(d,p) potential, we found that alanine inversion proceeded via previously unknown intermediates, 2-iminopropane-1,1-diol and 3-amino-3-methyloxiran-2-ol. The CG-HFB method accurately located transition states, aiding in the interpretation of complex reaction mechanisms. Thus, on the B3LYP∕6-31G(d,p) potential, the gas phase activation barriers for the inversion and acylation reactions were 50.5 and 39.9 kcal∕mol, respectively. These barriers determine the spontaneous loss of amino acid chirality and cleavage of peptide bonds in proteins. We conclude that the combined CG-HFB method further advances QM and QM∕MM studies of reaction mechanisms.
authors.affiliation: Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, United States Army Medical Research and Materiel Command, Fort Detrick, Maryland 21702, USA.
authors.forename: Ilja V
authors.initials: IV
authors.lastname: Khavrutskii
authors.forename: Jason B
authors.initials: JB
authors.lastname: Smith
authors.forename: Anders
authors.initials: A
authors.lastname: Wallqvist
mesh_terms: D000215:Acylation; D000409:Alanine / Q000737:chemistry*; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry; D011522:Protons; D011789:Quantum Theory; D013237:Stereoisomerism
chemical_list: D010455:Peptides; D011522:Protons; D000409:Alanine