Multi-Scale Approach for Self-Assembly and Protein Folding

Abstract

We develop a multi-scale approach to simulate hydrated nanobio systems under realistic conditions (e.g., nanoparticles and protein solutions at physiological conditions over time-scales up to hours). We combine atomistic simulations of water at bio-interfaces (e.g., proteins or membranes) and nano-interfaces (e.g., nanoparticles or graphene sheets) and coarse-grain models of hydration water for protein folding and protein design. We study protein self-assembly and crystallization, in bulk or under confinement, and the kinetics of protein adsorption onto nanoparticles, verifying our predictions in collaboration with several experimental groups. We try to find answers for fundamental questions (Why water is so important for life? Which properties make water unique for biological processes?) and applications (Can we design better drugs? Can we limit proteinaggregations causing Alzheimer? How to implement nanotheranostic?). Here we focus only on the two larger scales of our approach: (i) The coarse-grain description of hydrated proteins and protein folding at sub-nanometric length-scale and milliseconds-to-seconds time-scales, and (ii) the coarse-grain modeling of protein self-assembly on nanoparticles at 10-to-100 nm length-scale and seconds-to-hours time-scales. arXiv:1707.01065v1 [cond-mat.soft]

Membranes with different hydration levels: The interface between bound and unbound hydration water

“…They are part of our efforts to develop a multiscale approach to gain access to large scale and long time simulations of nanobio systems [48] where all the components are considered, at least at coarse-grained level, including water [49,50], proteins [51,52,53], proteins interfaces [54], protein-protein interactions [55,56] and membranes.…”

Protein Unfolding and Aggregation near a Hydrophobic Interface

“…Our results are potentially useful for the understanding of the mechanisms that control protein aggregation, a process that is associated with a growing number of neurodegenerative pathologies, including Alzheimer’s disease and Parkinson’s disease [ 52 , 53 ]. They represent the first step toward a multi-scale approach to study how to use nanostructured interfaces to regulate and, eventually, hamper pathological protein aggregation [ 54 ].…”

Protein Unfolding and Aggregation near a Hydrophobic Interface

“…Our results are potentially useful for the understanding of the mechanisms that control protein aggregation, a process that is associated with a growing number of neurodegenerative pathologies, including Alzheimer's disease and Parkinson's disease [52,53]. They represent the first step toward a multi-scale approach to study how to use nanostructured interfaces to regulate and, eventually, hamper pathological protein aggregation [54]. Funding: G.F. acknowledges the support of Spanish grant PGC2018-099277-B-C22 (MCIU/AEI /FEDER, UE), and the support by ICREA Foundation (ICREA Academia prize).…”