Hierarchical design of artificial proteins and complexes toward synthetic structural biology

Abstract

In multiscale structural biology, synthetic approaches are important to demonstrate biophysical principles and mechanisms underlying the structure, function, and action of bio-nanomachines. A central goal of "synthetic structural biology" is the design and construction of artificial proteins and protein complexes as desired. In this paper, I review recent remarkable progress of an array of approaches for hierarchical design of artificial proteins and complexes that signpost the path forward toward synthetic structural biology as an emerging interdisciplinary field. Topics covered include combinatorial and protein-engineering approaches for directed evolution of artificial binding proteins and membrane proteins, binary code strategy for structural and functional de novo proteins, protein nanobuilding block strategy for constructing nano-architectures, protein-metal-organic frameworks for 3D protein complex crystals, and rational and computational approaches for design/creation of artificial proteins and complexes, novel protein folds, ideal/optimized protein structures, novel binding proteins for targeted therapeutics, and self-assembling nanomaterials. Protein designers and engineers look toward a bright future in synthetic structural biology for the next generation of biophysics and biotechnology.

Conformational Characterization and Classification of Intrinsically Disordered Proteins by Native Mass Spectrometry and Charge‐State Distribution Analysis

“…These systems allow comparison of folded and unfolded proteins under identical solvent conditions, as well as comparison of disordered polypeptides with different sequence features, particularly hydropathy. Indeed, hydrophobic residues are much less represented, on average, in IDPs than globular proteins . Therefore, synthetic IDPs, as defined above, offer a tool to test the role of sequence hydropathy within the same conformational state and avoiding buffer effects.…”

“…Indeed, hydrophobic residues are much less represented, on average, in IDPs than globular proteins. [68] Therefore, synthetic IDPs, as defined above, offer a tool to test the role of sequence hydropathy within the same conformational state and avoiding buffer effects. This is relevant to the present discussion, since sequence hydrophobicity could play a role in the ESI mechanism.…”

Lectin engineering: the possible and the actual

“…These strategies are further categorized based on two criteria: first, whether they are based on combinatorial and protein engineering methods or rational and computational methods, and second where in the hierarchy of structures, i.e. primary, secondary, tertiary, quaternary and supra-quaternary structures, they focus [60]. From a statistical viewpoint, protein folding is quite unsuccessful (a success rate , 10 210 ) when using a random-sequence polypeptide library [61].…”

“…[60], typically one of 14 strategies is used, i.e. (i) random-sequence library-directed evolution, (ii) secondary structure element library, (iii) binary code, (iv) nanohedra, (v) protein nano-building block, (vi) metal-templated interface redesign, (vii) protein-metalorganic frameworks, (viii) parametrical design of a-helical coiled coil, (ix) fully automated sequence selection, (x) computational design of a novel globular protein fold, (xi) principles for designing ideal protein structures, (xii) protein design by tandem repeating a structural motif, (xiii) design of Supposed mechanism for the sugar-binding specificity change of ACG by a single amino acid substitution at Asn46.…”

Electrokinetic characterization of synthetic protein nanoparticles

“…Protein nanoparticles (PNPs) are useful for the loading of active therapeutic enzymes and show potential results to be used as vaccines [ 5 – 6 ]. Significant advances in self-assembled PNPs via protein engineering techniques have also been observed [ 7 – 8 ]. PNPs have successfully reached the clinic with nab-paclitaxel (Abraxane ® ), a PNP made of human serum albumin, which is being used for the treatment of metastatic breast cancer, non-small cell lung cancer, and pancreatic adenocarcinomas [ 9 ].…”