Free Energy Coefficients

The molecular mechanics-based and empirical terms are multiplied by coefficients that are determined by linear regression analysis of complexes with known 3D-structures and known binding free energies. In the equations on this page, these weights are W_vdW, W_H-bond, W_elec, W_desolv and W_tor. In AutoDock 4, these free energy weights, FE_coeff_vdW, FE_coeff_hbond, FE_coeff_estat, FE_coeff_desolv and FE_coeff_tors, can be set in the parameter file.

Molecular Mechanics Terms

• van der Waals

  ΔG_vdW = W_vdW ∑_{i, j} ( A_ij / r_ij¹² - B_ij / r_ij⁶ )

• Hydrogen Bonding

  ΔG_H-bond = W_H-bond ∑_{i, j} E(t) * ( C_ij / r_ij¹² - D_ij / r_ij¹⁰ + E_hbond )

• Electrostatics - see Coulomb's Law
  

  ΔG_elec = W_elec ∑_{i, j} ( q_i * q_j ) / ( ε(r_ij) * r_ij )

• Desolvation (AutoDock 3)
  

  ΔG_desolv = W_desolv ∑_{i (C), j} (S_i * V_j * exp ( -r_ij² / (2 * σ²) ) )

• see also AutoDock 4 Desolvation Free Energy for more details about the AutoDock 4 desolvation term.
  

Estimated Change in Torsional Free Energy when the Ligand goes from Unbound to Bound

• Torsional

  ΔG_tor = W_tor N_tor
  (where N_tor is the number of all rotatable bonds, excluding guanidinium and amide bonds etc.)

Complete equation:

Changing Atom Types and Parameters

Note that in AutoDock 4, there are more atom types allowed for the molecules, and these are specified in PDBQT-formatted files.

The default force-field parameters for these atom types can be overrided using the "parameter_file" command in the GPF and DPF. This command requires one argument, namely the filename of the ".dat" file that contains the linear free energy model's coefficients and the atom parameters; the default values can be found in "AD4_parameters.dat" which resides in the source code distribution. For more details, read the FAQs, Where do I set the AutoDock 4 force field parameters? and How do I add new atom types to AutoDock 4?.