Improving the Accuracy of Fitted Atomic Models in Cryo-EM Density Maps of Protein Assemblies Using Evolutionary Information from Aligned Homologous Proteins

Abstract

Cryo-Electron Microscopy (cryo-EM) has become an important technique to obtain structural insights into large macromolecular assemblies. However the resolution of the density maps do not allow for its interpretation at atomic level. Hence they are combined with high resolution structures along with information from other experimental or bioinformatics techniques to obtain pseudo-atomic models. Here, we describe the use of evolutionary conservation of residues as obtained from protein structures and alignments of homologous proteins to detect errors in the fitting of atomic structures as well as improve accuracy of the protein-protein interfacial regions in the cryo-EM density maps.

Tools for the cryo-EM gold rush: going from the cryo-EM map to the atomistic model

“…In this way, one can find biologically more meaningful solutions by sampling more relevant conformations with reduced simulation time. The use of evolutionary conservation of residues is already being used to detect incorrectly fitted proteins [ 103 , 104 ] in cryo-EM maps, to predict protein structures [ 105 , 106 ] and druggable interfaces of protein–protein interactions [ 107 ].…”

Biography of a scientist with strength, substance, sincerity and service: Late N. Srinivasan (1962-2021)

“…There were several surprising findings such as the structural effects of binding in parts away from protein-protein interface [ 26 ] and the interface residues harbouring both intra- and inter protein interactions [ 27 ]. NS's group started focussing on large protein assemblies [ 28 - 29 ] and on host-pathogen interactions as well [ 30 ]. NS became a Fellow of National Academy of Science India, Allahabad in the year 2009.…”