title: Protein Aggregation and Molecular Crowding: Perspectives From Multiscale Simulations.
abstract: Cells are extremely crowded environments, thus the use of diluted salted aqueous solutions containing a single protein is too simplistic to mimic the real situation. Macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, interactions with cognate biomolecules, and pathological aggregation. The latter phenomenon typically leads to the formation of amyloid fibrils that are linked to several lethal neurodegenerative diseases, but that can also play a functional role in certain organisms. The majority of molecular simulations performed before the last few years were conducted in diluted solutions and were restricted both in the timescales and in the system dimensions by the available computational resources. In recent years, several computational solutions were developed to get close to physiological conditions. In this review we summarize the main computational techniques used to tackle the issue of protein aggregation both in a diluted and in a crowded environment.
authors.affiliation: Laboratory of Bioinorganic Chemistry, University of Bologna, Bologna, Italy. Electronic address: francesco.musiani@unibo.it.
authors.forename: F
authors.initials: F
authors.lastname: Musiani
authors.affiliation: Applied Bioinformatics Group, University of Verona, Verona, Italy. Electronic address: alejandro.giorgetti@univr.it.
authors.forename: A
authors.initials: A
authors.lastname: Giorgetti
mesh_terms: D000465:Algorithms; D000818:Animals; D019295:Computational Biology; D003198:Computer Simulation; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism*; D008958:Models, Molecular; D066329:Protein Aggregates
chemical_list: D046911:Macromolecular Substances; D066329:Protein Aggregates
keywords: Atomistic simulations; Coarse-grained models; Discrete molecular dynamics; Enhanced sampling techniques; Molecular crowding; Molecular dynamics; Protein aggregation