Computations for interrogating protein complex architecture

How can we study inherently dynamic and heterogeneous architectures of protein complexes?

Most techniques struggle with heterogeneous systems, especially when lowly populated states are crucial for the molecular function.

Native mass spectrometry (MS), especially when coupled with ion mobility spectrometry (IM) has emerged as a powerful technique for studying macromolecular complexes in heterogeneous and dynamic systems.

The computational tools and methods required for data interpretation have not matched the advances on the experimental side however. We will realise some promising key concepts to complement IM-MS experiments with advanced computations.

We will 1) strengthen the connection between 3D structure and experiments by making a radically improved version of the Trajectory Method for IM calculations, 2) make use of existing vast databases of protein complex structures to develop a knowledge-based approach for predicting the overall architecture of unknown protein complexes, 3) deploy an efficient molecular dynamics setup based on the Fast Multipole Model that moves the current limitations for simulations of proteins under mass spectrometry conditions considerably, enabling investigations of important protein complexes at unprecedented timescales, and 4) explore the assembly of noro- and corona virus capsids using our methods together with experimental data, and assess how muck knowledge can be gained from IM-MS on such systems.