Abstract
We present a two-stage hybrid-resolution approach for rigid-body protein-protein docking. The first stage is carried out at low-resolution (15°) angular sampling. In the second stage, we sample promising regions from the first stage at a higher resolution of 6°. The hybrid-resolution approach produces the same results as a 6° uniform sampling docking run, but uses only 17% of the computational time. We also show that the angular distance can be used successfully in clustering and pruning algorithms, as well as the characterization of energy funnels. Traditionally the root-mean-square-distance is used in these algorithms, but the evaluation is computationally expensive as it depends on both the rotational and translational parameters of the docking solutions. In contrast, the angular distances only depend on the rotational parameters, which are generally fixed for all docking runs. Hence the angular distances can be pre-computed, and do not add computational time to the post-processing of rigid-body docking results.
Highlights
Protein-protein interactions are important for many fundamental cellular processes, and high-throughput proteomics studies have shown that most proteins interact with other proteins
In this work we explored the use of angular distance in proteinprotein docking to measure similarities of predictions
We showed such a scheme that on average reduces the computational cost of a docking run by a factor of six while maintaining the success rate and average hit count compared with a standard 6u docking run
Summary
Protein-protein interactions are important for many fundamental cellular processes, and high-throughput proteomics studies have shown that most proteins interact with other proteins. Starting from the unbound protein structures, computational protein-protein docking attempts to determine the structures of the bound complexes [1,2]. This challenging problem is usually approached in a stepwise fashion. The second stage accounts for conformational changes of the constituent proteins upon complex formation. Such conformational changes can involve only surface side chains, the backbones of surface loops, or even entire domains [15,16,17,18,19]
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