Integrative structural modelling using restraints derived from mass spectrometry

Maya Topf (primary)
Biological Sciences
Birkbeck
Konstantinos Thalassinos (secondary)
Structural Molecular Biology
University College London

Abstract

Determining structures of macromolecular assemblies is key to the mechanistic understanding of the cell. Due to the complexity of this task, it is often performed by a combination of multiple experimental techniques complemented by computational methods. We propose to develop a computational method for determining the architecture of dynamic assemblies at different levels of organisation using integrative modelling based on information from various mass spectrometry-based proteomic techniques. The method will be integrated into our general approach for assembly structure modelling (using primarily 3D-electron microscopy data) and will be tested on a number of protein assemblies, using both simulated and experimental data.


References

1. Thalassinos K, Pandurangan AP, Xu M, Alber F, Topf M. Conformational States of macromolecular assemblies explored by integrative structure calculation. (2013) Structure 21:1500-8

2. Pandurangan AP, Vasishtan D, Alber F, Topf M. γ-TEMPy: simultaneous fitting of components in 3D-EM maps of their assembly using a genetic algorithm. (2015) Structure 23:2365–2376.

3. Bullock JMA, Schwab J, Thalassinos K, Topf M. The importance of non-accessible crosslinks and solvent accessible surface distance in modelling proteins with restraints from crosslinking mass spectrometry. (2016) Mol Cell Proteomics. 15:10.1074/mcp.M116.058560, 2491–2500.

4. Zeev-Ben-Mordehai T, Vasishtan D, Hernandez A, Vollmer B, White P, Pandurangan AP, Siebert A, Topf M, Grünewald K.  Two distinct trimeric conformations of natively membrane-anchored full-length Herpes simplex virus 1 glycoprotein B. (2016) Proc Natl Acad Sci USA. 113:4176-4181.

5. Ashford P, Hernandez A, Greco TM, Buch A, Sodeik B, Cristea IM, Grünewald K, Shepherd A, Topf M. HVint: A strategy for identifying novel protein-protein interactions in herpes simplex virus type 1. (2016) Mol Cell Proteomics. 15:10.1074/mcp.M116.058552, 2939-2953.


BBSRC Area
Molecules, cells and industrial biotechnology
Area of Biology
MicrobiologyStructural Biology
Techniques & Approaches
BiochemistryBioinformaticsBiophysicsImage ProcessingMicroscopy / ElectrophysiologySimulation / Modelling