TITAN

TITAN generates and manipulates electric fields in biological systems to quantify intrinsic and applied electrostatic effects on enzymatic reactivity (PMID: 31568581).

Key Features:

• Electric Field Generation: Creates a range of external electric fields to probe their influence on biological systems.
• Quantification of Local Electric Fields: Quantifies intrinsic electric fields in proteins and other biomolecules using Coulomb's Law.
• Integration with Computational Methods: Supports coupling to quantum mechanics (QM), molecular mechanics (MM), QM/MM hybrid methods, and molecular dynamics simulations.

Scientific Applications:

• Enzymatic Reactivity Analysis: Elucidates the role of intrinsic and external electric fields in enzymatic reactions.
• Cytochrome P450 OleT_JE Studies: Applied to cytochrome P450 OleT_JE to study hydrogen transfer reactions (PMID: 31568581).
• Protein Matrix Effects: Demonstrates that the protein matrix in P450 OleT_JE acts as a moderate catalyst for hydrogen transfer.
• Electric Field Modulation: Shows that an oriented external electric field along the Fe─O bond in compound I significantly alters the reaction barrier, indicating modulation of enzymatic activity.
• Spin Density Correlation: Relates observed catalytic or inhibitory effects to changes in the calculated spin density on the oxygen atom.

Methodology:

Models and quantifies electric fields using Coulomb's Law and integrates those field calculations with QM, MM, QM/MM and molecular dynamics simulations.