Enhanced Thermostability of Glucose Oxidase through Computer-Aided Molecular Design

Ning, Xiaoyan; Yuan, Tiantian; Li, Qingbin; Tian, Jian; Guan, Weishi; Liu, Bo; Zhang, Wei; Xu, Xinxin; Zhang, Yuhong

doi:10.3390/ijms19020425

Cited by 23 publications

(12 citation statements)

References 30 publications

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“…For α-gurjunene, a lower RMSF value was noticed, followed by aromadendrene and allo-aromadendrene. Lower RMSF values suggest more excellent stability and the natural compound's possibility to inhibit the target molecule [37,46]. Changes in ligand positioning have also been monitored by the ligand RMSD measurement, as shown in Figure 5c.…”

Section: Simulationsmentioning

confidence: 99%

A Computational Study to Identify Potential Inhibitors of SARS-CoV-2 Main Protease (Mpro) from Eucalyptus Active Compounds

et al. 2020

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was found to be a severe threat to global public health in late 2019. Nevertheless, no approved medicines have been found to inhibit the virus effectively. Anti-malarial and antiviral medicines have been reported to target the SARS-CoV-2 virus. This paper chose eight natural eucalyptus compounds to study their binding interactions with the SARS-CoV-2 main protease (Mpro) to assess their potential for becoming herbal drugs for the new SARS-CoV-2 infection virus. In-silico methods such as molecular docking, molecular dynamics (MD) simulations, and Molecular Mechanics Poisson Boltzmann Surface Area (MM/PBSA) analysis were used to examine interactions at the atomistic level. The results of molecular docking indicate that Mpro has good binding energy for all compounds studied. Three docked compounds, α-gurjunene, aromadendrene, and allo-aromadendrene, with highest binding energies of −7.34 kcal/mol (−30.75 kJ/mol), −7.23 kcal/mol (−30.25 kJ/mol), and −7.17 kcal/mol (−29.99 kJ/mol) respectively, were simulated with GROningen MAchine for Chemical Simulations (GROMACS) to measure the molecular interactions between Mpro and inhibitors in detail. Our MD simulation results show that α-gurjunene has the strongest binding energy of −20.37 kcal/mol (−85.21 kJ/mol), followed by aromadendrene with −18.99 kcal/mol (−79.45 kJ/mol), and finally allo-aromadendrene with −17.91 kcal/mol (−74.95 kJ/mol). The findings indicate that eucalyptus may be used to inhibit the Mpro enzyme as a drug candidate. This is the first computational analysis that gives an insight into the potential role of structural flexibility during interactions with eucalyptus compounds. It also sheds light on the structural design of new herbal medicinal products against Mpro.

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Section: Simulationsmentioning

confidence: 99%

A Computational Study to Identify Potential Inhibitors of SARS-CoV-2 Main Protease (Mpro) from Eucalyptus Active Compounds

et al. 2020

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“…Enzyme engineering has also been employed to improve the specific activity, glucose affinity and O2 sensitivity of GOx including ultrahigh-throughput screening. [24][25][26][27][28]29,30] But, most of those efforts were performed in homogeneous solution using O2 as an electron acceptor and are not suitable for electrochemical applications. In addition, other parameters such as the interaction between GOx and redox mediators were not taken into account.…”

Section: Introductionmentioning

confidence: 99%

Engineering glucose oxidase for bioelectrochemical applications

Mano

2019

Bioelectrochemistry

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There is still a growing interest in developing glucose sensors using glucose oxidase.Since 2012, over 1000 papers are published every year, while efficient commercial sensors exist on the market. Among those glucose sensors, few have been thought and well-engineered and do not solve the problems associated with glucose oxidase; among which the O2 sensitivity of the enzyme or the competition between O2 and redox mediators for GOx's electrons. Enzyme engineering has been employed to solve those issues but screening GOx in homogeneous solution with O2 as an electron acceptor is not suitable. Very few reports describe the specific reengineering of GOx for electrochemical applications and are the subject of this review. It starts with a brief presentation of glucose oxidase and presents the recent progress in glucose oxidase reengineering by highlighting the kind of engineering/mutations performed to increase its electron transfer rate to electrode surfaces and, to decrease its O2 sensitivity. In addition, the review highlights the need to develop new screening methods involving electrochemical probing, essential to develop the next generation of glucose sensors; specific to glucose, O2 independent, biocompatible and stable over 2 weeks.

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“…Similar to RMSD, the root mean square fluctuation (RMSF) was used to analyze the difference in atomic position between a conformation of a biological macromolecule at a certain time and a reference conformation. The larger the RMSF of a residue of a protein, the higher its flexibility [42]. As shown in Figure 8B, ACE had five major flexible regions located at the 62–71, 115–117, 256–260, 306–312, 397–401, 434–437, 460–464, 503–506, and 577–579 residues, which were the peripheral random coil structures, away from the active center (Figure S2).…”

Section: Resultsmentioning

confidence: 99%

Discovery of Novel Angiotensin-Converting Enzyme Inhibitory Peptides from Todarodes pacificus and Their Inhibitory Mechanism: In Silico and In Vitro Studies

Song

Zhu

et al. 2019

IJMS

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In order to rapidly and efficiently excavate antihypertensive ingredients in Todarodes pacificus, its myosin heavy chain was hydrolyzed in silico and the angiotensin-converting enzyme (ACE) inhibitory peptides were predicted using integrated bioinformatics tools. The results showed the degree of hydrolysis (DH) theoretically achieved 56.8% when digested with papain, ficin, and prolyl endopeptidase (PREP), producing 126 ACE inhibitory peptides. By predicting the toxicity, allergenicity, gastrointestinal stability, and intestinal epithelial permeability, 30 peptides were finally screened, of which 21 had been reported and 9 were new. Moreover, the newly discovered peptides were synthesized to evaluate their in vitro ACE inhibition, showing Ile-Ile-Tyr and Asn-Pro-Pro-Lys had strong effects with a pIC50 of 4.58 and 4.41, respectively. Further, their interaction mechanisms and bonding configurations with ACE were explored by molecular simulation. The preferred conformation of Ile-Ile-Tyr and Asn-Pro-Pro-Lys located in ACE were successfully predicted using the appropriate docking parameters. The molecular dynamics (MD) result indicated that they bound tightly to the active site of ACE by means of coordination with Zn(II) and hydrogen bonding and hydrophobic interaction with the residues in the pockets of S1 and S2, resulting in stable complexes. In summary, this work proposed a strategy for screening and identifying antihypertensive peptides from Todarodes pacificus.

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Enhanced Thermostability of Glucose Oxidase through Computer-Aided Molecular Design

Cited by 23 publications

References 30 publications

A Computational Study to Identify Potential Inhibitors of SARS-CoV-2 Main Protease (Mpro) from Eucalyptus Active Compounds

A Computational Study to Identify Potential Inhibitors of SARS-CoV-2 Main Protease (Mpro) from Eucalyptus Active Compounds

Engineering glucose oxidase for bioelectrochemical applications

Discovery of Novel Angiotensin-Converting Enzyme Inhibitory Peptides from Todarodes pacificus and Their Inhibitory Mechanism: In Silico and In Vitro Studies

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