Identification of dynamic structural domains in proteins, analysis of local bond flexibility and application for interpretation of NMR experiments

Abstract

A novel theoretical methodology is described that allows the identification of dynamic structural domains and the analysis of local flexibility in proteins. The methodology employs a multiscale approach that combines definition of essential collective coordinates based on the covariance analysis of molecular dynamics trajectories, construction of the Mori projection operator with these essential coordinates and analysis of the corresponding generalised Langevin equations. The domains are associated with relatively stable regions in the protein, whereas off-domain regions are relatively soft. The applications include the domain coarse-graining and characterisation of the local flexibility in protein G and prion proteins. The results are compared with published NMR experiments. The methodology is apt to provide rigorous dynamic scores and characterisation tools for structural biology, bioinformatics and rational drug design.

Keywords:

• protein coarse-graining
• multiscale modelling
• generalised Langevin dynamics
• interpretation of NMR measurements