A Protocol for the Design of Protein and Peptide Nanostructure Self-Assemblies Exploiting Synthetic Amino Acids

Abstract

In recent years there has been increasing interest in nanostructure design based on the self-assembly properties of proteins and polymers. Nanodesign requires the ability to predictably manipulate the properties of the self-assembly of autonomous building blocks, which can fold or aggregate into preferred conformational states. The design includes functional synthetic materials and biological macromolecules. Autonomous biological building blocks with available 3D structures provide an extremely rich and useful resource. Structural databases contain large libraries of protein molecules and their building blocks with a range of sizes, shapes, surfaces, and chemical properties. The introduction of engineered synthetic residues or short peptides into these building blocks can greatly expand the available chemical space and enhance the desired properties. Herein, we summarize a protocol for designing nanostructures consisting of self-assembling building blocks, based on our recent works. We focus on the principles of nanostructure design with naturally occurring proteins and synthetic amino acids, as well as hybrid materials made of amyloids and synthetic polymers.

Computational drug design of novel COVID-19 inhibitor

“…The electrostatic charge was neutralized by adding counter ions using the LeaP program of AMBER ver.11. After minimization, heating and equilibration, the production MD phase was carried out at 300 K for 1 ns with a time step of 1 ps (picoseconds) using the constant volume and temperature (NVT) ensemble and the Particle Mesh Ewald algorithm for the calculation of electrostatic interactions (Haspel, Zheng, Aleman, Zanuy, & Nussinov, 2017). The initial velocity of atoms was generated at 100 K in heating phase with a Maxwellian distribution and maintained.…”

Atomic Scale Structure of Self‐Assembled Lipidated Peptide Nanomaterials

“…[6] The most widely studied class of lipidated peptide consists of one alkyl tail that is generally attached to the N-terminus which can self-assemble in water resulting in nanostructures [12,[19][20][21][22][23][24] that are amenable to a wide range of bioactive ligands attached at the C-terminus. [11,25] Unlike 𝛼-peptides that have attracted most attention, [2,[26][27][28][29][30][31][32][33][34][35] the more recently discovered 𝛽-peptide scaffolds are of particular interest because of their rapid selfassembly in water, resistance to proteolysis and mechanical stability. [36] 𝛽-peptide scaffolds can additionally be chemically modified at the monomer level to carry different "payloads" of varying size and bioactivity -without affecting self-assembly -while being cell interactive, and most importantly, 𝛽-peptides are modular in design, allowing the flexibility required to achieve optimal mechanical, biorecognition and nanotopographic properties, as a platform to modulate or support cell behavior in any setting.…”

“…Unlike α‐peptides that have attracted most attention, [ 2,26–35 ] the more recently discovered β‐peptide scaffolds are of particular interest because of their rapid self‐assembly in water, resistance to proteolysis and mechanical stability. [ 36 ] β‐peptide scaffolds can additionally be chemically modified at the monomer level to carry different “payloads” of varying size and bioactivity – without affecting self‐assembly ‐ while being cell interactive, and most importantly, β‐peptides are modular in design, allowing the flexibility required to achieve optimal mechanical, biorecognition and nanotopographic properties, as a platform to modulate or support cell behavior in any setting.…”

High-power Terahertz Waves for a Recycle System of Amyloid Fibrils

“…The amyloid is originally wellknown to be involved in various biological phenomena such as the onset of serious amyloidosis 6,7 , biofilm formation 8,9 , biosynthesis of pigment melanin 10 , protection of eggshells 11 , supramolecular assembly in the body structures 12 , and gene expressions 13 . On the contrary, the amyloid-like proteins and peptides can be on-demand designed based on the solid-phase peptide synthesis technique [14][15][16] , which allows us to develop various amyloid materials such as rigid scaffolds for cell cultivation and tissue engineering 17,18 , artificial capsules and hydrogels for drug delivery systems 19,20 , and functional nanofilms for microorganism adhesion and protein crystallization for medical purposes 21,22 . Therefore, a versatile approach for structural control of the amyloid fibrils will be useful for remodeling of the fibrous format in various biomaterial fields.…”