Existing protein-ligand docking methods computationally screen thousands to millions of organic molecules against protein structures, trying to find those with complementary shapes and highest binding free energies. To allow large molecular databases to be screened rapidly, simple and approximative scoring functions are used as a fast filter, resulting in low hit rates. Therefore, docking hit l...

BACKGROUND The number of high-resolution structures of pharmacologically relevant membrane proteins has been strongly increasing. This makes computing relative affinities of chemically similar compounds binding to a membrane protein possible in order to guide decision making in drug design. However, the preparation step of such calculations is time-consuming and complex. METHODS We extended t...

Absolute free energies of hydration (ΔGhyd) for more than 500 neutral and charged compounds have been computed, using Poisson-Boltzmann (PB) and Generalized Born (GB) continuum methods plus a solvent-accessible surface area (SA) term, to evaluate the accuracy of eight simple point-charge models used in molecular modeling. The goal is to develop improved procedures and protocols for protein-liga...

In the drug discovery process, accurate methods of computing the affinity of small molecules with a biological target are strongly needed. This is particularly true for molecular docking and virtual screening methods, which use approximated scoring functions and struggle in estimating binding energies in correlation with experimental values. Among the various methods, MM-PBSA and MM-GBSA are em...

MM-PBSA is a post-processing end-state method to calculate free energies of molecules in solution. MMPBSA.py is a program written in Python for streamlining end-state free energy calculations using ensembles derived from molecular dynamics (MD) or Monte Carlo (MC) simulations. Several implicit solvation models are available with MMPBSA.py, including the Poisson-Boltzmann Model, the Generalized ...