title: Computational smart polymer design based on elastin protein mutability.
abstract: Soluble elastin-like peptides (ELPs) can be engineered into a range of physical forms, from hydrogels and scaffolds to fibers and artificial tissues, finding numerous applications in medicine and engineering as "smart polymers". Elastin-like peptides are attractive candidates as a platform for novel biomaterial design because they exhibit a highly tunable response spectrum, with reversible phase transition capabilities. Here, we report the design of the first virtual library of elastin-like protein models using methods for enhanced sampling to study the effect of peptide chemistry, chain length, and salt concentration on the structural transitions of ELPs, exposing associated molecular mechanisms. We describe the behavior of the local molecular structure under increasing temperatures and the effect of peptide interactions with nearest hydration shell water molecules on peptide mobility and propensity to exhibit structural transitions. Shifts in the magnitude of structural transitions at the single-molecule scale are explained from the perspective of peptide-ion-water interactions in a library of four unique elastin-like peptide systems. Predictions of structural transitions are subsequently validated in experiment. This library is a valuable resource for recombinant protein design and synthesis as it elucidates mechanisms at the single-molecule level, paving a feedback path between simulation and experiment for smart material designs, with applications in biomedicine and diagnostic devices.
authors.affiliation: Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Tarakanova
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Huang
authors.affiliation: School of Life and Environmental Sciences and Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Weiss
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
authors.affiliation: Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: mbuehler@mit.edu.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Buehler
mesh_terms: D003198:Computer Simulation; D004549:Elastin / Q000138:chemical synthesis* / Q000737:chemistry / Q000235:genetics*; D006860:Hydrogen Bonding; D009154:Mutation / Q000235:genetics*; D009391:Nephelometry and Turbidimetry; D012492:Salts / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013696:Temperature; D014867:Water / Q000737:chemistry
chemical_list: D012492:Salts; D012997:Solvents; D014867:Water; D004549:Elastin
keywords: Elastin-like peptide (ELP); Inverse temperature transition; Peptide-water interaction; Protein simulation library; Single-molecule