Molecular Dynamics Simulations for Three-Dimensional Structures of Orotate Phosphoribosyltransferases Constructed from a Simplified Amino Acid Set

Kato, Koichi; Nakayoshi, Tomoki; Kurimoto, Eiji; Oda, Akifumi

doi:10.1021/acsomega.0c01012

Cited by 5 publications

(3 citation statements)

References 37 publications

(79 reference statements)

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“…We have previously performed molecular dynamics (MD) simulations to clarify the conformation of proteins using only a limited number of amino acids [ 24 , 25 , 26 ]. MD simulations of [GADV]-peptides, in which G, A, D, and V are randomly arranged, can form a protein secondary structure [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of the Addition of the Fifth Amino Acid to [GADV]-Protein on the Three-Dimensional Structure

Kato

Nakayoshi

Oyaizu

et al. 2023

Life

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The [GADV]-protein, consisting only of glycine (G), alanine (A), aspartic acid (D), and valine (V), is frequently studied as a candidate for a primitive protein that existed at the beginning of life on Earth. The number of proteogenic amino acids increased during evolution, and glutamic acid may have been added as the fifth amino acid. In this study, we used molecular dynamics simulations to estimate the conformation of random peptides when glutamate is added to G, A, D, and V ([GADVE]), when leucine is added ([GADVL]), and when the frequency of alanine is doubled ([GADVA]). The results showed that the secondary structure contents of the [GADVE]-peptide and [GADVL]-peptide were higher than that of the [GADVA]-peptide. Although the [GADVL]-peptide had a higher secondary structure formation ability than the [GADVE]-peptide, it was less water soluble, suggesting that it may not be a primitive protein. The [GA(D/E)V]-peptide with G:A:D:V:E = 2:2:1:2:1 according to the occurrence ratio in the codon table also increased the secondary structure contents compared to the [GADV]-peptide, indicating that the addition of glutamic acid increased the structure formation ability of the primitive protein candidates.

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Section: Introductionmentioning

confidence: 99%

Effect of the Addition of the Fifth Amino Acid to [GADV]-Protein on the Three-Dimensional Structure

Kato

Nakayoshi

Oyaizu

et al. 2023

Life

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“…Comprehending the interaction between the biological membrane and CN is essential for the further use of CN for medical applications. Molecular Dynamics (MD) simulations provide the three-dimensional view from systems at the atomic level, which is difficult to obtain using experimental methods 20 . Previously, we using MD simulations to evaluate the loading of two anticancer drugs on the functional and pristine CN nanosheets 21 .…”

Section: Introductionmentioning

confidence: 99%

Molecular interpretation of the carbon nitride performance as a template for the transport of anti-cancer drug into the biological membrane

Zaboli

Raissi

Farzad

2021

Sci Rep

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Evaluation of interaction mechanism between 2-dimensional (2D) nanomaterials and cell membranes is a critical issue in providing guidelines for biomedical applications. Recent progress in computer-aided molecular design tools, especially molecular dynamics (MD) simulation, afford a cost-effective approach to achieving this goal. In this work, based on this hypothesis, by utilizing theoretical methods including MD simulation and free energy calculations, a process is evaluated in which the Doxorubicin (DOX)-loaded onto carbon nitride (CN) nanosheet faced with bilayer membrane. It should be mentioned that to achieve an efficient CN-based drug delivery system (DDS), in the first place, the intermolecular interaction between the carrier and DOX is investigated. The obtained results show that the DOX prefers a parallel orientation with respect to the CN surface via the formation of π–π stacking and H-bond interactions. Furthermore, the adsorption energy value between the drug and the carrier is evaluated at about − 312 kJ/mol. Moreover, the investigation of the interaction between the CN-DOX complex and the membrane reveals that due to the presence of polar heads in the lipid bilayer, the contribution of electrostatic energy is higher than the van der Waals energy. The global minimum in free energy surface of the DDS is located between the head groups of the cell membrane. Overall, it can be concluded that the CN nanosheet is a suitable candidate for transfer and stabilize DOX on the membrane.

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“…The MD simulations for CYP2A6.25, CYP2A6.26, CYP2A6.35, CYP2A6.36, and CYP2A6.37 were performed to investigate the effects of mutation combinations on three-dimensional (3D) structures. MD simulations were variable methods to investigate the structural features of mutant proteins including CYP [ 29 , 30 , 31 , 32 , 33 , 34 ]. For comparison, the simulation of the wild type (CYP2A6.1) was also performed.…”

Section: Introductionmentioning

confidence: 99%

Deciphering Structural Alterations Associated with Activity Reductions of Genetic Polymorphisms in Cytochrome P450 2A6 Using Molecular Dynamics Simulations

Kato

Nakayoshi

Nokura

et al. 2021

IJMS

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Cytochrome P450 (CYP) 2A6 is a monooxygenase involved in the metabolism of various endogenous and exogenous chemicals, such as nicotine and therapeutic drugs. The genetic polymorphisms in CYP2A6 are a cause of individual variation in smoking behavior and drug toxicities. The enzymatic activities of the allelic variants of CYP2A6 were analyzed in previous studies. However, the three-dimensional structures of the mutants were not investigated, and the mechanisms underlying activity reduction remain unknown. In this study, to investigate the structural changes involved in the reduction in enzymatic activities, we performed molecular dynamics simulations for ten allelic mutants of CYP2A6. For the calculated wild type structure, no significant structural changes were observed in comparison with the experimental structure. On the other hand, the mutations affected the interaction with heme, substrates, and the redox partner. In CYP2A6.44, a structural change in the substrate access channel was also observed. Those structural effects could explain the alteration of enzymatic activity caused by the mutations. The results of simulations provide useful information regarding the relationship between genotype and phenotype.

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Molecular Dynamics Simulations for Three-Dimensional Structures of Orotate Phosphoribosyltransferases Constructed from a Simplified Amino Acid Set

Cited by 5 publications

References 37 publications

Effect of the Addition of the Fifth Amino Acid to [GADV]-Protein on the Three-Dimensional Structure

Effect of the Addition of the Fifth Amino Acid to [GADV]-Protein on the Three-Dimensional Structure

Molecular interpretation of the carbon nitride performance as a template for the transport of anti-cancer drug into the biological membrane

Deciphering Structural Alterations Associated with Activity Reductions of Genetic Polymorphisms in Cytochrome P450 2A6 Using Molecular Dynamics Simulations

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