Multiscale simulation-guided design of enzyme bioconjugates with enhanced catalysis

Hong, Xiaobin; Cholko, Timothy; Chang, Chia‐en A.; Wheeldon, Ian

doi:10.1016/j.checat.2022.09.018

Cited by 5 publications

(5 citation statements)

References 29 publications

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“…Furthermore, rigorous statistical mechanics theory can be applied to relate the ensemble of microscopic configurations with macroscopic thermodynamic properties. Classical molecular simulations have been applied to study a wide range of biomaterial systems such as supramolecular biopolymer, DNA-based bioconjugate, self-assembling peptides, − carbohydrate-based biomaterials, , and lipid membranes. − …”

Section: Methodsmentioning

confidence: 99%

Computational Design of Peptides for Biomaterials Applications

Wang

Stebe

Fuente-Núñez

et al. 2023

ACS Appl. Bio Mater.

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Computer-aided molecular design and protein engineering emerge as promising and active subjects in bioengineering and biotechnological applications. On one hand, due to the advancing computing power in the past decade, modeling toolkits and force fields have been put to use for accurate multiscale modeling of biomolecules including lipid, protein, carbohydrate, and nucleic acids. On the other hand, machine learning emerges as a revolutionary data analysis tool that promises to leverage physicochemical properties and structural information obtained from modeling in order to build quantitative protein structure−function relationships. We review recent computational works that utilize state-of-the-art computational methods to engineer peptides and proteins for various emerging biomedical, antimicrobial, and antifreeze applications. We also discuss challenges and possible future directions toward developing a roadmap for efficient biomolecular design and engineering.

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Section: Methodsmentioning

confidence: 99%

Computational Design of Peptides for Biomaterials Applications

Wang

Stebe

Fuente-Núñez

et al. 2023

ACS Appl. Bio Mater.

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“…is based that fast and highly effective immobilization, and then isolation and purification of the enzyme itself occurs. The emerging coordination bonds between metal atoms in the carrier and nitrogen atoms in the imidazole rings of the polyhistidine sequence in the protein molecule make it possible to anchor the enzyme on the carrier quite firmly [ 2 , 22 , 23 ] and use it for a long time, in such an immobilized form, for the destruction of OPCs ( Table 1 , [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]). Of particular interest are such immobilization variants for the stabilization and repeated use of the enzyme in the degradation of OPC-polluting water systems [ 22 , 23 ].…”

Section: Stabilization Of Hexa-histidine-containing Oph For Opc Hydro...mentioning

confidence: 99%

“…It is interesting to note that an increase in the DNA concentration relative to QD-OPH and the creation of dense composites led to an increase in the enzymatic reaction rate by 12.5 times [ 43 ]. It should be noted that, in principle, the use of DNA molecules modified for their use as bioscaffolds for the enzyme under discussion has proven to be very good in terms of an effective means of improving the catalytic characteristics of the obtained biocatalysts even in the absence of QD [ 44 ].…”

Section: Stabilization Of Hexa-histidine-containing Oph For Opc Hydro...mentioning

confidence: 99%

“…However, the spectrum of the substrates of this enzyme is not limited to OPCs [ 2 , 19 , 20 ], and therefore, the options for its stabilization and immobilization for use in other hydrolytic reactions remain extremely interesting. A lot of parameters of biocatalytic systems can be predicted in silico: the interaction of the enzyme with novel substrates [ 4 , 6 ], the interaction of the enzyme microenvironment/partner with substrates [ 43 ], the binding of enzymes with individual polymers [ 46 ], etc. Prospectively, computer modeling may allow the designing of the necessary catalytic system on a turnkey basis.…”

Section: Stabilization Of Hexa-histidine-containing Oph For Opc Hydro...mentioning

confidence: 99%

“…It should be emphasized that the catalytic activity was studied against different substrates (methyl parathion [ 23 , 25 , 26 , 27 , 28 , 29 , 30 , 37 , 46 , 47 ], paraoxon [ 31 , 32 , 33 , 34 , 41 , 42 , 43 , 44 , 46 , 47 ], malathion [ 36 , 44 ], methyl–paraoxon [ 38 ], coumaphos [ 39 , 40 ], chlorphyryphos [ 45 ], VX [ 8 , 29 ], etc.) under different conditions (mixing and its absence [ 25 , 32 , 44 , 45 ], flow reactor [ 23 , 82 ]) at different temperatures and pH values [ 44 ].…”

Section: Comparative Analysis Of Biocatalysts Based On Immobilized/st...mentioning

confidence: 99%

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Carrier Variety Used in Immobilization of His6-OPH Extends Its Application Areas

et al. 2023

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Organophosphorus hydrolase, containing a genetically introduced hexahistidine sequence (His6-OPH), attracts the attention of researchers by its promiscuous activity in hydrolytic reactions with various substrates, such as organophosphorus pesticides and chemical warfare agents, mycotoxins, and N-acyl homoserine lactones. The application of various carrier materials (metal-organic frameworks, polypeptides, bacterial cellulose, polyhydroxybutyrate, succinylated gelatin, etc.) for the immobilization and stabilization of His6-OPH by various methods, enables creation of biocatalysts with various properties and potential uses, in particular, as antidotes, recognition elements of biosensors, in fibers with chemical and biological protection, dressings with antimicrobial properties, highly porous sorbents for the degradation of toxicants, including in flow systems, etc. The use of computer modeling methods in the development of immobilized His6-OPH samples provides in silico prediction of emerging interactions between the enzyme and immobilizing polymer, which may have negative effects on the catalytic properties of the enzyme, and selection of the best options for experiments in vitro and in vivo. This review is aimed at analysis of known developments with immobilized His6-OPH, which allows to recognize existing recent trends in this field of research, as well as to identify the reasons limiting the use of a number of polymer molecules for the immobilization of this enzyme.

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Molecular mechanics studies of factors affecting overall rate in cascade reactions: Multi‐enzyme colocalization and environment

Kaushik,

Hung,

Chang

2024

Protein Science

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Millions of years of evolution have optimized many biosynthetic pathways by use of multi‐step catalysis. In addition, multi‐step metabolic pathways are commonly found in and on membrane‐bound organelles in eukaryotic biochemistry. The fundamental mechanisms that facilitate these reaction processes provide strategies to bioengineer metabolic pathways in synthetic chemistry. Using Brownian dynamics simulations, here we modeled intermediate substrate transportation of colocalized yeast–ester biosynthesis enzymes on the membrane. The substrate acetate ion traveled from the pocket of aldehyde dehydrogenase to its target enzyme acetyl‐CoA synthetase, then the substrate acetyl CoA diffused from Acs1 to the active site of the next enzyme, alcohol‐O‐acetyltransferase. Arranging two enzymes with the smallest inter‐enzyme distance of 60 Å had the fastest average substrate association time as compared with anchoring enzymes with larger inter‐enzyme distances. When the off‐target side reactions were turned on, most substrates were lost, which suggests that native localization is necessary for efficient final product synthesis. We also evaluated the effects of intermolecular interactions, local substrate concentrations, and membrane environment to bring mechanistic insights into the colocalization pathways. The computation work demonstrates that creating spatially organized multi‐enzymes on membranes can be an effective strategy to increase final product synthesis in bioengineering systems.

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Multiscale simulation-guided design of enzyme bioconjugates with enhanced catalysis

Cited by 5 publications

References 29 publications

Computational Design of Peptides for Biomaterials Applications

Computational Design of Peptides for Biomaterials Applications

Carrier Variety Used in Immobilization of His6-OPH Extends Its Application Areas

Molecular mechanics studies of factors affecting overall rate in cascade reactions: Multi‐enzyme colocalization and environment

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