How should ligand structure be represented for docking with Lead Finder – as a 2D or 3D structure? Are both representations acceptable?

A ligand structure must contain 3D coordinates for all of its atoms! Ideally, the 3D structure of a ligand must be optimized with one of the available 3D optimization programs. In addition, a 3D structure must be carefully prepared with respect to its protonation state and tautomeric forms of the ligand.

What file formats of ligand structure are acceptable for docking with Lead Finder?

The acceptable file formats are: mol, mol2, and sdf.

How should protein structure be prepared for docking with Lead Finder?

A protein structure must contain 3D coordinates for all of its atoms, including hydrogens! Note that the protons must be attached to a protein structure at a particular pH at which ligand binding is evaluated. You should be careful in preparing a full-atomic protein structure for docking studies. At present, Lead Finder provides its own software module for preparation of protein molecules for docking. This module is designed to add hydrogen atoms to appropriate heavy atoms in protein structures or homology models at a given pH (see the Solutions section for details).

What file formats of protein structure are acceptable for docking with Lead Finder?

The acceptable file formats are: mol2, pdb, gro.

What is the difference between VS-score and dG-score?

The VS-score is designed to rank-order ligands according to their predicted activity (binding potency) in virtual screening experiments. The VS-score may not correlate with measurable parameters such as free energy of binding. The VS-score is useful only for separating active compounds from inactive ones. On the contrary, the dG-score is designed to estimate the free energy of ligand binding when you know that this particular ligand is a true binder. We recommend that you use the VS-score to select a desired number of top-ranking active compounds in a virtual screening experiment and use the dG-score to estimate free energy of binding for these ligands.

What is the difference between docking and screening regimes and which one should I use?

The screening regime is 2-4 times faster than docking regime, however its docking success rate appears to be about 5% lower. The accuracy of dG prediction has proven to be practically identical for both regimes. You should choose a regime on the basis of available computing capacity and particular task requirements.