TITAN: A Code for Modeling and Generating Electric Fields-Features and Applications to Enzymatic Reactivity.

Area of Science:

• Computational chemistry
• Biophysics
• Biochemistry

Background:

• Understanding electric fields in biological systems is crucial for deciphering molecular mechanisms.
• Quantifying local electric fields and simulating external field effects aids in studying enzymatic reactions.

Purpose of the Study:

• To introduce the elecTric fIeld generaTion And maNipulation (TITAN) code for generating and analyzing electric fields.
• To investigate the influence of local and external electric fields on enzymatic reactions, specifically hydrogen transfer in cytochrome P450 OleT_JE.

Main Methods:

• Development of the versatile TITAN computational code based on Coulomb's Law.
• Coupling TITAN with standard computational chemistry software for quantum mechanics (QM), molecular mechanics (MM), QM/MM, and molecular dynamics.
• Application of TITAN to study hydrogen transfer in cytochrome P450 OleT_JE, including simulations with oriented external electric fields.

Main Results:

• The TITAN code successfully generates diverse external electric fields and quantifies local electric fields in biological systems.
• The protein matrix of P450 OleT_JE exhibits moderate catalytic activity in hydrogen transfer.
• An oriented external electric field applied along the Fe─O bond of compound I significantly impacted the reaction barrier, correlating with spin density changes.

Conclusions:

• The TITAN code provides a powerful tool for simulating electric field effects in biological contexts.
• External electric fields can modulate enzymatic activity, offering potential for controlling biochemical processes.
• The study highlights the interplay between protein environment, local electric fields, and external field manipulations in enzymatic catalysis.