Using the fast fourier transform in binding free energy calculations

Area of Science:

• Computational chemistry
• Molecular modeling
• Biophysics

Background:

• Implicit ligand theory defines binding free energy via the binding potential of mean force (BPMF).
• BPMF calculation traditionally involves averaging interaction energies over ligand-receptor configurations.

Purpose of the Study:

• To develop an efficient computational method for calculating standard binding free energies.
• To apply the fast Fourier transform (FFT) algorithm to accelerate BPMF evaluation.

Main Methods:

• Utilized the fast Fourier transform (FFT) to efficiently compute binding potential of mean force (BPMF).
• Calculated interaction energies by discretely translating rigid ligand configurations across rigid receptor conformations.
• Applied the method to T4 lysozyme and 141 small organic molecules.

Main Results:

• Achieved good agreement between FFT-calculated binding free energies and previous alchemical calculations.
• Demonstrated high correlation coefficients (R≈0.9 and R≈0.8) with established methods for flexible systems.
• Showcased the FFT algorithm's applicability to rigorous binding free energy calculations.

Conclusions:

• The FFT-based approach offers an efficient and accurate alternative for binding free energy calculations.
• This method represents a significant advancement in applying FFT algorithms beyond molecular docking.
• The findings open new avenues for computational drug design and molecular interaction studies.