Exploring chemical reaction mechanisms through harmonic Fourier beads path optimization

Area of Science:

• Computational Chemistry
• Chemical Reaction Dynamics
• Biophysical Chemistry

Background:

• Studying chemical reactions on complex potential energy surfaces requires efficient computational methods.
• Quantum mechanical (QM) and hybrid QM/molecular mechanical (QM/MM) methods are computationally demanding for reaction path optimization.

Purpose of the Study:

• To enhance the efficiency of path optimization for chemical reactions on QM and QM/MM potential energy surfaces.
• To investigate the mechanisms of biologically relevant reactions, including amino acid inversion and alcohol acylation.

Main Methods:

• Application of the harmonic Fourier beads (HFB) path optimization method.
• Integration of HFB with conjugate gradient (CG) optimization to create the CG-HFB method.
• Study of L- to D-alanine amino acid inversion and alcohol acylation reactions using the CG-HFB method.

Main Results:

• The CG-HFB method efficiently optimized reaction paths on computationally demanding potentials.
• Unexpected reaction intermediates, such as 2-iminopropane-1,1-diol and 3-amino-3-methyloxiran-2-ol, were identified for alanine inversion.
• Accurate location of transition states facilitated the interpretation of complex reaction mechanisms.
• Gas phase activation barriers for alanine inversion and alcohol acylation were determined to be 50.5 and 39.9 kcal/mol, respectively.

Conclusions:

• The combined CG-HFB method significantly advances the study of reaction mechanisms using QM and QM/MM approaches.
• The identified reaction pathways and barriers provide insights into the spontaneous loss of amino acid chirality and peptide bond cleavage.