Rh. Zhou et al., New linear interaction method for binding affinity calculations using a continuum solvent model, J PHYS CH B, 105(42), 2001, pp. 10388-10397
A new linear interaction energy (LIE) method based on a continuum solvent s
urface generalized Born (SGB) model is proposed for protein-ligand binding
affinity calculations. The new method SGB-LIE is about 1 order of magnitude
faster than previously published LIE methods based on explicit solvents. I
t has been applied to several binding sets: HEPT analogues binding to HIV-1
reverse transcriptase (20 ligands), sulfonamide inhibitors binding to huma
n thrombin (seven ligands), and various ligands binding to coagulation fact
or Xa (eight ligands). The SGB-LIE predictions and cross-validation results
show that about 1.0 kcal/mol accuracy is achievable for binding sets with
as many as 20 ligands, e.g., for the HIV-1 RT binding set, RMS errors of 1.
07 and 1.20 kcal/mol are achieved for LIE fitting and leave-one-out cross v
alidation, respectively, with correlation coefficients r(2) equal to 0.774
and 0.717. We have also explored various techniques for the LIE underlying
conformation space sampling, including molecular dynamics and hybrid Monte
Carlo methods, and the final results show that comparable binding energies
can be obtained no matter which sampling technique is used.