Flexible fitting to cryo-electron microscopy maps with coarse-grained elastic network models

Abstract

Cryo-electron microscopy has become an important tool for protein structure determination in recent decades. Since proteins may exist in multiple conformational states, combining high resolution X-ray or NMR structures with cryo-electron microscopy maps is a useful approach to obtain proteins in different functional states. Flexible fitting methods used in cryo-electron microscopy aim to obtain an unknown protein conformation from a high resolution structure and a cryo-electron microscopy map. Since all-atom flexible fitting is computationally expensive, many efficient flexible fitting algorithms that utilize coarse-grained elastic network models have been proposed. In this study, we investigated performance of three coarse-grained elastic network model-based flexible fitting methods (EMFF, iModFit, NMFF) using 25 protein pairs at four resolutions. This study shows that the application of coarse-grained elastic network models to flexible fitting of cryo-electron microscopy maps can provide fast and fruitful models of various conformational states of proteins.

Keywords:

• Coarse-grained elastic network model
• normal mode
• flexible fitting
• cryo-electron microscopy map
• protein conformation

Acknowledgements

The numerical calculations reported in this paper were performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA Resources). The author thank them for providing superb computational resources and technical help.