Local heterogeneity analysis of crystallographic and cryo-EM maps using shell-approximation

Abstract

In X-ray crystallography and cryo-EM, experimental maps can be heterogeneous, showing different level of details in different regions. In this work we interpret heterogeneity in terms of two parameters, assigned individually for each atom, combining the conventional atomic displacement parameter with the resolution of the atomic image in the map. We propose a local real-space procedure to estimate the values of these heterogeneity parameters, assuming that a fragment of the density map and atomic positions are given. The procedure is based on an analytic representation of the atomic image, as a function of the inhomogeneity parameters and atomic coordinates. In this article, we report the results of the tests both with maps simulated and those derived from experimental data. For simulated maps containing regions with different resolutions, the method determines the local map resolution around the atomic centers and the values of the displacement parameter with reasonable accuracy. For experimental maps, obtained as a Fourier synthesis of a given global resolution, estimated values of the local resolution are close to the global one, and the values of the estimated displacement parameters are close to the respective values of the closest atoms in the refined model. Shown successful applications of the proposed method to experimental crystallographic and cryo-EM maps can be seen as a practical proof of method.