Prediction of 3D structure of protein-ligand complexes

By: Biomoltech  09-12-2011
Keywords: Competitive Programs

Ligand Docking

Lead Finder predicts 3D structure of non-covalent and covalently bound protein-ligand complexes by docking a flexible ligand to a static protein structure. The remarkable efficiency of Lead Finder is based on a unique conformational search algorithm and high accuracy scoring function to evaluate the free energy of protein-ligand binding (see the

section).

Accuracy of protein-ligand docking has been validated on a set of 407 protein-ligand complexes that appears to be the most extensive benchmarking study of such kind. This test set comprises test sets of such docking programs as

,

,

,

,

,

that allows fair and straightforward comparison of Lead Finder to the original predictions by the competitive programs. As can be seen from our

, Lead Finder has outperformed all competitive programs on their native test sets, with docking success rates ranging from 80.0% on Glide XP and FlexX test sets to 96.0% on Surflex and MolDock test sets.

Lead Finder has intuitive program interface that is easy to configure and use. While many configuration options are available to end users to fine-tune docking calculations, two calculation regimes, docking and screening, have been created to provide the optimum balance between the speed of calculations and the accuracy of predictions. Docking regime is slower but a bit more accurate. Screening regime is fine-tuned to achieve fastest performance at the cost of slight decrease in docking accuracy (see the

section for more details).

The speed of docking calculations has been extensively benchmarked both on the test set of 407 experimentally characterized protein-ligand complexes and in real-life virtual screening experiments of large commercial libraries of compounds against various drug targets. In our trials, docking of a single compound has taken 30-60 seconds on average in the more accurate docking regime, and 10-20 seconds in the faster virtual screening regime (see the

section for more details).

Keywords: Competitive Programs

Other products and services from Biomoltech

09-12-2011

Lead Finder - a software solution for virtual screening and molecular docking

Accuracy of protein-ligand docking has been validated on a set of 407 protein-ligand complexes, which appears to be the most extensive benchmarking study of such kind at present. However, virtual screening, ligand docking and estimation of binding energy of protein-ligand interaction are clearly the three primary application areas for Lead Finder.


09-12-2011

Pre-docking Preparation of Protein Structures

Lead Finder uses an original theoretical approach to assign optimal ionization states of protein residues at arbitrary pH conditions, which is based on the recently introduced screened coulomb potential model. SCP theory treats microenvironment-dependent energy of electrostatic interactions as a function of local hydrophilicity and degree of solvent exposure.


09-12-2011

Estimation of Free Energy of Binding in Protein-Ligand Complexes

This functionality is novel to docking software since binding energy calculation is usually done in separate software packages that are based on various theoretical approaches including free energy perturbation, linear interaction energy, etc.


09-12-2011

Virtual Screening of Libraries of Chemical Compounds

To accelerate processing of large libraries in virtual screening experiments, Lead Finder employs a special modification of the docking algorithm called screening mode. During virtual screening each ligand from a library is docked to a target protein, and ligands are rank-ordered according to their binding potencies.