Abstract
By reaching near-atomic resolution for a wide range of specimens, single-particle cryo-EM structure determination is transforming structural biology. However, the necessary calculations come at large computational costs, which has introduced a bottleneck that is currently limiting throughput and the development of new methods. Here, we present an implementation of the RELION image processing software that uses graphics processors (GPUs) to address the most computationally intensive steps of its cryo-EM structure determination workflow. Both image classification and high-resolution refinement have been accelerated more than an order-of-magnitude, and template-based particle selection has been accelerated well over two orders-of-magnitude on desktop hardware. Memory requirements on GPUs have been reduced to fit widely available hardware, and we show that the use of single precision arithmetic does not adversely affect results. This enables high-resolution cryo-EM structure determination in a matter of days on a single workstation.
Highlights
With the advent of direct-electron detectors and advanced methods of image processing, structural characterisation of macromolecular complexes to nearatomic resolution is feasible using single-particle electron cryo-microscopy (Li et al, 2013; Bai et al, 2013)
The most demanding computation in regularised likelihood optimisation is the comparison of projections of the reference structure along many different orientations with thousands or millions of individual particle images (Fig. 1)
By utilising fast-access data structures known as textures, on-demand projection achieves faster execution compared to reading pre-calculated projections from memory
Summary
With the advent of direct-electron detectors and advanced methods of image processing, structural characterisation of macromolecular complexes to nearatomic resolution is feasible using single-particle electron cryo-microscopy (cryo-EM) (Li et al, 2013; Bai et al, 2013). This has caused a rapid gain in its popularity, two technological factors still limit wide applicability of cryo-EM as a standard tool for structural biology. Partly due to the steep increase in demand, access to high-end microscopes is limited This is being addressed with acquisition of new equipment in a large number of departments worldwide, as well as the establishment of shared infrastructures (Saibil et al, 2015). The work presented here addresses this second problem, to the end of drastically reducing the computational time and investment necessary for cryo-EM structure determination
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