Self Assembly of Disordered Folded Multiphase Proteins by Computer Simulations

Abstract

Disordered proteins have the capacity to self-assemble from random coils to partial or complete folded structures. Such combination of amorphous/ordered phases within the protein structure is determined by the aminoacid sequence as well as enviromental factors, such as flow or confinement, and it is expected that the proportion of each phase would play a role in the activity and biological function of the protein. Nevertheless, modeling the molecular arrangement of disordered/folded structures poses a challenge and it has been possible only for few short fragments or individual proteins. For macromolecular complexes, computationally analyzing properties such as dynamics, mechanics or heat transfer requires taking the polymeric nature of chain entanglements into account. We devised a new approach based on an existing collapsing-annealing Molecular Dynamics protocol [1] for building amorphous phases of long disordered protein chains. We adapted it to also include structured phases such as beta-sheet units, by steering parts of the protein chains into the experimentally known conformations. As a proof-of-concept, we successfully set up a model of 100 intrinsically disordered chains each comprising 500 aminoacids of silk spidroin. This resulted in a compact protein-only system (20 nm)ˆ3 in size. Then, we introduced silk crystalline units based on x-ray scattering data, highlighting that our newly-develop protocol can handle composite materials with partial structure as well. Our full detail atomistic structure is the most comprehensive silk model computationally studied to date, up to our knowledge. We believe our approach to be valuable for a wide range of Molecular Dynamics simulations, in which the disordered polymeric component of proteins dominates in the assembly or biomaterial.[1] Cruz-Chu, E. R et al. Faraday Discussions (2009) 143, 47-62.