Optimizing weighting functions for cryo-electron microscopy

The frequency-dependent signal to noise ratio of cryo-electron microscopy data varies dramatically with the frequency and with the type of the data. During different steps of data processing, data with distinct SNR are used for calculations. Thus, specific weighting function based on the particular SNR should be designed to optimize the corresponding calculation. Here, we deduced these weighting functions by maximizing the signal to noise ratio of cross correlated coefficients. Some of our weighting functions for refinement resemble that used in the existing software packages. However, weighting functions we deduced for motion correction, particle picking and the refinement with overlapping densities differ from those employed by existing programs. Our new weighting functions may improve the calculation in these steps.