Enhanced sampling of protein conformational states for dynamic cross-docking within the protein-protein docking server SwarmDock.

The formation of specific protein-protein interactions is often a key to a protein's function. During complex formation, each protein component will undergo a change in the conformational state, for some these changes are relatively small and reside primarily at the sidechain level; however, others may display notable backbone adjustments. One of the classic problems in the protein-docking field is to be able to a priori predict the extent of such conformational changes. In this work, we investigated three protocols to find the most suitable input structure conformations for cross-docking, including a robust sampling approach in normal mode space. Counterintuitively, knowledge of the theoretically best combination of normal modes for unbound-bound transitions does not always lead to the best results. We used a novel spatial partitioning library, Aether Engine (see Supplementary Materials), to efficiently search the conformational states of 56 receptor/ligand pairs, including a recent CAPRI target, in a systematic manner and selected diverse conformations as input to our automated docking server, SwarmDock, a server that allows moderate conformational adjustments during the docking process. In essence, here we present a dynamic cross-docking protocol, which when benchmarked against the simpler approach of just docking the unbound components shows a 10% uplift in the quality of the top docking pose.

On the use of programmable hardware and reduced numerical precision in earth-system modeling.

Programmable hardware, in particular Field Programmable Gate Arrays (FPGAs), promises a significant increase in computational performance for simulations in geophysical fluid dynamics compared with CPUs of similar power consumption. FPGAs allow adjusting the representation of floating-point numbers to specific application needs. We analyze the performance-precision trade-off on FPGA hardware for the two-scale Lorenz '95 model. We scale the size of this toy model to that of a high-performance computing application in order to make meaningful performance tests. We identify the minimal level of precision at which changes in model results are not significant compared with a maximal precision version of the model and find that this level is very similar for cases where the model is integrated for very short or long intervals. It is therefore a useful approach to investigate model errors due to rounding errors for very short simulations (e.g., 50 time steps) to obtain a range for the level of precision that can be used in expensive long-term simulations. We also show that an approach to reduce precision with increasing forecast time, when model errors are already accumulated, is very promising. We show that a speed-up of 1.9 times is possible in comparison to FPGA simulations in single precision if precision is reduced with no strong change in model error. The single-precision FPGA setup shows a speed-up of 2.8 times in comparison to our model implementation on two 6-core CPUs for large model setups.