Mesoscale Modelling of Biomolecules using Continuum Mechanics

Biophysical techniques that provide structural information at the mesoscale, such as cryo-electron microscopy and 3D tomography, are now sufficiently mature that they merit their own online repository called the EMDataBank (EMDB). We have developed a continuum mechanics description of proteins which uses this new experimental data as input to the simulations. The model is a Finite Element algorithm which we have generalised to include thermal fluctuations, and which is therefore known as Fluctuating Finite Element Analysis (FFEA). While conventional molecular dynamics simulations provide a trajectory in which each individual atomic position fluctuates, an FFEA trajectory shows how the overall shape of the protein changes due to thermal agitation. We have used FFEA to show that the crowded environment of the axoneme impedes the thermal fluctuations of the largest cytoskeletal motor dynein, and have used our model to calculate the reach of the motor in situ. Our modelling highlights the importance of understanding the 3D architecture of biological structures at the mesoscale.