Computer-aided protein-ligand binding predictions are a valuable help in drug discovery. Protein-ligand docking programs generally consist of two main components: a scoring function and a search algorithm. It is of interest to evaluate the intrinsic performance of scoring functions, independently of conformational exploration, to understand their strengths and weaknesses and suggest improvements. The comparative assessment of scoring functions (CASF) provides such an evaluation. Here we add the AutoDock and Vina scoring functions to the CASF-2013 benchmark. We find that these popular, free software docking programs are generally in the first half (AutoDock) and first quarter (Vina) among all methods tested in CASF-2013. Vina is the best of all methods in terms of docking power. We also find that ligand minimization has an important impact, reducing the performance difference between AutoDock and Vina.

We describe an automated procedure for protein design, implemented in a flexible software package, called Proteus. System setup and calculation of an energy matrix are done with the XPLOR modeling program and its sophisticated command language, supporting several force fields and solvent models. A second program provides algorithms to search sequence space. It allows a decomposition of the system into groups, which can be combined in different ways in the energy function, for both positive and negative design. The whole procedure can be controlled by editing 2-4 scripts. Two applications consider the tyrosyl-tRNA synthetase enzyme and its successful redesign to bind both O-methyl-tyrosine and D-tyrosine. For the latter, we present Monte Carlo simulations where the D-tyrosine concentration is gradually increased, displacing L-tyrosine from the binding pocket and yielding the binding free energy difference, in good agreement with experiment. Complete redesign of the Crk SH3 domain is presented. The top 10000 sequences are all assigned to the correct fold by the SUPERFAMILY library of Hidden Markov Models. Finally, we report the acid/base behavior of the SNase protein. Sidechain protonation is treated as a form of mutation; it is then straightforward to perform constant-pH Monte Carlo simulations, which yield good agreement with experiment. Overall, the software can be used for a wide range of application, producing not only native-like sequences but also thermodynamic properties with errors that appear comparable to other current software packages.