ATP-Magnesium Coordination: Protein Structure-Based Force Field Evaluation and Corrections.

Area of Science:

• Biochemistry and molecular dynamics simulations.
• Computational chemistry and biophysics.
• Structural biology and molecular recognition.

Background:

• Adenosine triphosphate (ATP)·magnesium (Mg²⁺) is crucial for biochemical processes.
• Two primary Mg²⁺-phosphate coordination geometries exist, with high energy barriers between them.
• Accurate force fields are essential for simulating ATP·Mg²⁺ structure and energetics.

Purpose of the Study:

• To evaluate and correct force field descriptions of ATP·Mg²⁺ coordination energetics.
• To assess the accuracy of Amber and CHARMM force fields for ATP·Mg²⁺ simulations.
• To improve the predictive power of atomistic simulations for biochemical systems involving ATP.

Main Methods:

• Utilized enhanced sampling schemes to overcome slow transition dynamics.
• Performed configurational free energy calculations.
• Validated simulations against diverse ATP·Mg²⁺-protein complex structures and experimental data.

Main Results:

• Identified significant discrepancies between Amber and CHARMM force fields in predicting coordination modes.
• Quantified systematic force field biases by comparing with experimental observations.
• Developed additive corrections to force field energies, achieving close agreement with experimental data.

Conclusions:

• Corrected force fields accurately predict ATP·Mg²⁺ coordination modes.
• While CHARMM parameters show bias towards extended triphosphate forms, overall energy landscapes align with experimental and PDB data.
• The evaluation and correction approach is broadly applicable to other molecular systems in biomolecular simulations.