Improving the Efficiency of Protein–Ligand Binding Free-Energy Calculations by System Truncation

Improving the Efficiency of Protein-Ligand Binding Free-Energy Calculations by System Truncation.

We have studied whether the efficiency of alchemical free-energy calculations with the Bennett acceptance ratio method of protein-ligand binding energies can be improved by simulating only part of the protein. To this end, we solvated the full protein in a spherical droplet with a radius of 46 Å, surrounded by a vacuum. Then, we systematically reduced the size of the droplet and at the same tim...

Improving efficiency of protein–ligand binding free-energy calculations by system truncation

We have studied whether the efficiency of alchemical free-energy calculations with the Bennett acceptance ratio method of protein–ligand binding energies can be improved by simulating only a part of the protein. To this end, we solvated the full protein in a spherical droplet with a radius of 46 Å, surrounded by vacuum. Then, we systematically reduced the size of the droplet and at the same tim...

Improving the efficiency and reliability of free energy perturbation calculations using overlap sampling methods

A challenge in free energy calculation for complex molecular systems by computer simulation is to obtain a reliable estimate within feasible computational time. In this study, we suggest an answer to this challenge by exploring a simple method, overlap sampling (OS), for producing reliable free-energy results in an efficient way. The formalism of the OS method is based on ensuring sampling of i...

Free energy calculations and ligand binding.

Using the fast fourier transform in binding free energy calculations.

According to implicit ligand theory, the standard binding free energy is an exponential average of the binding potential of mean force (BPMF), an exponential average of the interaction energy between the unbound ligand ensemble and a rigid receptor. Here, we use the fast Fourier transform (FFT) to efficiently evaluate BPMFs by calculating interaction energies when rigid ligand configurations fr...