Team:UCL/Model
Modelling
We employed two distinct modelling approaches to inform our project: structural and dynamic.
Our structural model, called MEND (Model of Encapsulin aNd DARPin), helped to inform our design of full encapsulin-DARPin assemblies. MEND helped to select the type of encapsulin and the length of DARPin-encapsulin linker needed to achieve: (i) unimpeded formation of our drug delivery vesicles and (ii) efficient interaction with the target receptor. We used PyMol, Discovery Studio and GROMACS to develop MEND and the validity of MEND was assessed along the way by experts in the field.
Our dynamic model, called cellCONOMY, allowed us to compare in vivo and in vitro protein yields. We wrote cellCONOMY to simulate, on one hand, the limited number of ribosomes per cell and the metabolic stress caused by heterologous protein expression or, on the other hand, the yields of cell free protein expression systems. Both in vivo and in vitro components of cellCONOMY were fitted with the lab data on cell growth and protein yields and then the model was used to predict production of a desired construct.