Open AccessEngineering the entropy-driven free-energy landscape of a dynamic nanoporous protein assembly
Author(s) -
Robert Alberstein,
Yuta Suzuki,
Francesco Paesani,
F.A. Tezcan
Publication year - 2018
Publication title -
nature chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.996
H-Index - 232
eISSN - 1755-4349
pISSN - 1755-4330
DOI - 10.1038/s41557-018-0053-4
Subject(s) - conformational entropy , energy landscape , chemistry , molecular dynamics , chemical physics , nanotechnology , entropy (arrow of time) , self assembly , protein engineering , protein structure , computational chemistry , molecule , materials science , physics , biochemistry , organic chemistry , quantum mechanics , enzyme
De novo design and construction of stimuli-responsive protein assemblies that predictably switch between discrete conformational states remains an essential but highly challenging goal in biomolecular design. We previously reported synthetic, two-dimensional protein lattices self-assembled via disulfide bonding interactions, which endows them with a unique capacity to undergo coherent conformational changes without losing crystalline order. Here, we carried out all-atom molecular dynamics simulations to map the free-energy landscape of these lattices, validated this landscape through extensive structural characterization by electron microscopy and established that it is predominantly governed by solvent reorganization entropy. Subsequent redesign of the protein surface with conditionally repulsive electrostatic interactions enabled us to predictably perturb the free-energy landscape and obtain a new protein lattice whose conformational dynamics can be chemically and mechanically toggled between three different states with varying porosities and molecular densities.