Less is more
Nanopores are biosensing tools with incredible potential for diagnostics.Though these proteins occur naturally in nature, they require careful engineering and design to be able to detect diagnostically relevant biomarkers.In this thesis we have developed several computational approaches to assist nanopore engineering efforts.
One such nanopore is the funnel-shaped "FraC", a pore that has been used extensively for detecting several types of biomarkers.We hypothesized that when FraC is made shorter, the shape of the pore changes in a way that changes its biosensing properties.To support this hypothesis we performed molecular simulations that show the change in shape as the pore gets shortened.When these short pores are produced in the lab and tested, they indeed behave differently to the original pore.
Another sensing challenge for nanopores lies in sensing peptides; small bits of protein that are often markers for disease.Due to their flexible nature, it is hard to predict the result of a peptide detection experiment.As such, we present a simulation workflow to study the nanopore sensing process of peptides, which enables us to make more accurate predictions about the detection results.Because nanopores are rather large molecules, this requires a specialized setup to be able to do effectively.The flexible nature of the peptides poses an additional challenge, which we address using a simulation technique that attempts to simulate such flexibility more efficiently.While the results are promising, more work is needed to improve the method.