Multi-scale modelling of amyloid formation from unfolded proteins using a set of theory derived rate constants

Traditional simulation and analysis of amyloid aggregation kinetics has involved the examination of a single lumped parameter taken to reflect the total mass of protein in amyloid form. However use of increasingly sophisticated multi-experimental strategies capable of providing information on the structure of the growing fibril at the mesoscopic and atomistic level, has put extra information within the experimenterʹs reach. Although such data can be presented empirically, its incorporation into a theoretical model is more problematic due to scaling issues associated with modern day approaches which fall into either the particle based or statistical based categories. Here we present a coarse grained multi-scale simulation of irreversible amyloid formation that straddles this simulation divide by using a set of theory derived size and conformation specific rate constants to simulate the kinetic evolution of the amyloid fibril population. This approach represents a potentially profitable simulation/analytical strategy that will help to probe more deeply into the underlying molecular driving forces behind the phenomenon of amyloid formation.