Large-Scale Assessment of Binding Free Energy Calculations in Active Drug Discovery Projects

Virtual screening of integrase inhibitors by large scale binding free energy calculations: the SAMPL4 challenge

As part of the SAMPL4 blind challenge, filtered AutoDock Vina ligand docking predictions and large scale binding energy distribution analysis method binding free energy calculations have been applied to the virtual screening of a focused library of candidate binders to the LEDGF site of the HIV integrase protein. The computational protocol leveraged docking and high level atomistic models to im...

Advances in binding free energies calculations: QM/MM-based free energy perturbation method for drug design.

Multiple approaches have been devised and evaluated to computationally estimate binding free energies. Results using a recently developed Quantum Mechanics (QM)/Molecular Mechanics (MM) based Free Energy Perturbation (FEP) method suggest that this method has the potential to provide the most accurate estimation of binding affinities to date. The method treats ligands/inhibitors using QM while u...

Free energy calculations and ligand binding.

Binding Free Energy Calculations for Lead Optimization: Assessment of Their Accuracy in an Industrial Drug Design Context.

Correctly ranking compounds according to their computed relative binding affinities will be of great value for decision making in the lead optimization phase of industrial drug discovery. However, the performance of existing computationally demanding binding free energy calculation methods in this context is largely unknown. We analyzed the performance of the molecular mechanics continuum solve...

Large scale free energy calculations for blind predictions of protein-ligand binding: the D3R Grand Challenge 2015

We describe binding free energy calculations in the D3R Grand Challenge 2015 for blind prediction of the binding affinities of 180 ligands to Hsp90. The present D3R challenge was built around experimental datasets involving Heat shock protein (Hsp) 90, an ATP-dependent molecular chaperone which is an important anticancer drug target. The Hsp90 ATP binding site is known to be a challenging targe...