A highly accurate model of protein-ligand interaction is critically important for successful docking simulations. Lead Finder's scoring functions are based on a semi-empiric molecular mechanical functional that explicitly accounts for various types of molecular interactions. Individual energy contributions are scaled with empiric coefficients to produce three scoring functions tailored for:

• accurate binding energy predictions;
• correct energy-ranking of docked ligand poses;
• correct rank-ordering of active and inactive compounds in virtual screening experiments.

The first scoring function has been designed to perform accurate estimation of the free energy of protein-ligand binding for a given structure of protein-ligand complex. For this reason, this scoring function has been named dG-scoring function, or simply dG-score. Experimentally determined structure of a protein-ligand complex, or a modeled structure obtained by docking and/or molecular dynamical studies can be used as input for binding energy estimation with dG-scoring function. The scaling coefficients for this function have been derived by fitting calculated binding energies to the experimental values for a set of 100 protein-ligand complexes with known 3D-structure and experimentally measured binding constants. The quality of the resultant dG-scoring function has been independently assessed on an additional set of 230 experimentally characterized protein-ligand complexes. For details of the benchmarking studies, see the Binding energy prediction section.

The second scoring function has been called ranking scoring function. This function is used for ranking of ligand poses obtained during a docking run. The purpose of this scoring function is to provide the highest score to the correct (experimentally observed) ligand pose. Parameterization (choice of scaling coefficients) of this scoring function was specifically aimed at achieving the maximum docking success rate, i.e. the maximum number of top-scored poses with correct geometry. For details of the benchmarking studies, see the Docking Success Rate section.

The third scoring function has been designed to produce maximum efficiency in virtual screening experiments. This scoring function assigns higher scores to active ligands (true binders) than to inactive ones. This scoring function type has been named virtual screening or VS-scoring function. More information about the performance of VS-scoring function can be found in the Virtual Screening Performance section.

The detailed description of the Lead Finder scoring functions can be downloaded as a PDF document.