We thank the experimentalists who supplied the targets and the CAPRI committee for organizing these difficulties and for evaluating submitted predictions

We thank the experimentalists who supplied the targets and the CAPRI committee for organizing these difficulties and for evaluating submitted predictions. == Recommendations ==. IRAD == Introduction == The Crucial Assessment of PRedicted Interactions (CAPRI) experiment has been an important driving force for the development of methods for the prediction of proteinprotein BKI-1369 structures.1Our laboratory has participated since the earliest rounds of CAPRI, using the ZDOCK algorithm and refinement scoring functions.25In this paper we report our results from rounds 20 to 26, which were held between 2010 and 2012 (Table I). == Table I. == Summary of the CAPRI rounds and our overall performance. Rounds 20 and 21 (targets 4345) and targets 55 and 56 were scoring-only and are not listed. Round 25 was cancelled. A template for the entire complex was available and docking was not needed. Docking three linked domains, of which two were unbound and one was homology modeled. Scoring combined with target 49. The three possible interfaces were assessed separately; our acceptable models were for CBM13-Fn3. The ZDOCK program for protein-protein docking was launched approximately 10 years ago.6,7ZDOCK uses Fast Fourier Transform (FFT) methods to perform an exhaustive search for potential binding modes of two component proteins. The proteins are kept rigid, and the six-dimensional (6D) conformation space is usually separated into 3 translational degrees of freedom (1.2 sampling) and three rotational degrees of freedom (6 or 15 degree sampling). For each angle combination only the best scoring translation is usually kept, resulting in 3,600 or 54,000 predictions for 15 degree or 6 degree angular sampling, respectively. Numerous versions of the ZDOCK algorithm were released, and the latest uses the IFACE statistical potential that was developed in our lab as well.8In addition to ZDOCK we developed a series of scoring functions for reranking docking results,911protein design,12and protein-protein binding free energy prediction.13 Since our most recent BKI-1369 report around the overall performance of ZDOCK in the CAPRI experiment,5we have published several algorithmic developments related to protein-protein docking. BKI-1369 First, we released a new version of the ZDOCK program, ZDOCK 3.0.2, which uses a new 3D convolution library.14Instead of using a 3D FFT, we now use a series of 1D FFTs, which allows the calculation of vacant grid points to be avoided. In combination with additional overall performance improvements, ZDOCK 3.0.2 represents a 5-fold Gpc4 speedup over our previous version ZDOCK 3.0, with exactly the same accuracy. We also developed a hybrid-resolution approach that led to further speedup.15We first perform a 15 degree angular sampling docking run. The top 400 (about 10%) predictions are selected, and we carry out a 6 degree angular sampling run only for those angle combinations that are within 10 degree of any of the 400 predictions. This approach reduces the search space dramatically, requiring only 10% of the full 6 degree sampling. Because the angular distances can be precomputed and do not add to the computational cost, we obtain a 6-fold speedup compared with the standard approach. The hit rates and success rates of the full hybrid-resolution and standard methods are, however, virtually indistinguishable. ZDOCK 3.0.2 and the hybrid-resolution can be applied simultaneously, resulting in a 30-fold speedup over the standard ZDOCK BKI-1369 3.0 algorithm. We also tested the use of angular distance for clustering docking solutions and the exploration of energy landscapes, and found that results are the same as obtained using RMSD distances, but with significant speedup.13 The use of FFT in docking requires the scoring functions to be expressed in the form of correlations, which are therefore more limiting than the BKI-1369 scoring functions of other molecular modeling methods. This is partially resolved by re-ranking the rigid-body docking solutions using more sophisticated scoring functions. Recently we developed the IRAD function, 10with the novel aspect that it combined atom-based and residue-based.