Implementing new algorithms dealing with conformational heterogeneity in single particle cryo-EM analysis

In order to deal with symmetry-mismatch within complexes, we have developed a local single particle with particle segmentation analysis method thus significantly improving the resolution of heterogeneous complex. Applying this method, we helped our collaborator Prof. Sen-Fang Sui’s group at Tsinghua University to discovery the SNAP complex’s mechanism to disassemble SNARE complex in membrane fusion. We have also developed focal heterogeneity classification algorithm in the structural analysis of human Dicer’s and yeast Exosome’s conformational flexibility and conformational distribution which provided important mechanistic insight to our understanding of these macromolecules.

Zhou Q, Huang X, Sun S, Li X, Wang HW*, Sui SF*. (2015) Cryo-EM structure of SNAP-SNARE assembly in 20S particle. Cell Research, 25:551-560 (*co-corresponding authors)