Improved constrained optimization method for reaction-path determination in the generalized hybrid orbital quantum...

Area of Science:

• Computational Chemistry
• Biochemistry
• Reaction Mechanism Studies

Background:

• Nudged elastic band (NEB) and string methods are common for reaction path calculations but struggle with accurate force generation.
• Constrained optimization with locally updated planes (CO-LUP) offers advantages for quantum mechanical/molecular mechanical (QM/MM) systems but has limitations in accuracy and image distribution.
• Accurate reaction path determination is crucial for understanding chemical reactions and enzymatic processes.

Purpose of the Study:

• To introduce modifications to the CO-LUP scheme to overcome limitations in reaction path calculations.
• To improve the accuracy and efficiency of determining reaction pathways, particularly in QM/MM systems.
• To provide a more reliable method for studying complex chemical reactions and enzyme mechanisms.

Main Methods:

• Modified CO-LUP scheme incorporating improved tangent estimation (from NEB), energy-weighted image redistribution, and reduced constraints.
• Testing on alanine dipeptide isomerization (without QM/MM) to compare accuracy and efficiency with the string method.
• Application to enzyme-catalyzed reactions: chorismate mutase (CM) and cAMP-dependent protein kinase (PKA) using generalized hybrid orbital QM/MM.

Main Results:

• The modified CO-LUP method demonstrates accuracy and efficiency comparable to the string method for alanine dipeptide isomerization.
• Calculations for CM and PKA reveal reaction energy barriers and pathways consistent with experimental and previous computational findings.
• The PKA reaction mechanism was elucidated as associative with a late proton transfer, aligning with recent NEB results.

Conclusions:

• The three modifications significantly enhance the CO-LUP scheme for accurate and efficient reaction path calculations.
• The improved CO-LUP method is a robust tool for studying complex reaction mechanisms in both small molecules and enzymatic systems.
• This work offers a valuable alternative for computational chemists and biochemists investigating reaction dynamics.