Ab initio structure solution of proteins at atomic resolution using charge-flipping techniques and cloud computing

Abstract

Large protein structures at atomic resolution can be solved in minutes using charge-flipping techniques operating on hundreds of virtual machines (computers) on the Amazon Web Services cloud-computing platform driven by the computer programs TOPAS or TOPAS-Academic at a small financial cost. The speed of operation has allowed charge-flipping techniques to be investigated and modified, leading to two strategies that can solve a large range of difficult protein structures at atomic resolution. Techniques include the use of space-group symmetry restraints on the electron density as well as increasing the intensity of a randomly chosen high-intensity electron-density peak. It is also shown that the use of symmetry restraints increases the chance of finding a solution for low-resolution data. Finally, a flipping strategy that negates `uranium atom solutions' has been developed for structures that exhibit such solutions during charge flipping.