International Journal of Molecular Sciences

Editorial

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3 pages, 173 KiB

Open AccessEditorial

Special Issue “2nd Edition: Advances in Molecular Simulation”

by Małgorzata Borówko

Int. J. Mol. Sci. 2023, 24(2), 1491; https://doi.org/10.3390/ijms24021491 - 12 Jan 2023

Viewed by 1121

Abstract

Molecular simulation is becoming a standard tool for researchers working in different fields, such as physics, chemistry, material science, biology, medicine, engineering, and many others [...] Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

Research

Jump to: Editorial

22 pages, 9257 KiB

Open AccessArticle

The Effects of One-Point Mutation on the New Delhi Metallo Beta-Lactamase-1 Resistance toward Carbapenem Antibiotics and β-Lactamase Inhibitors: An In Silico Systematic Approach

by Van-Thanh Tran, Viet-Hung Tran, Dac-Nhan Nguyen, Tran-Giang-Son Do, Thanh-Phuong Vo, Thi-Thao-Nhung Nguyen, Phuong Nguyen Hoai Huynh and Khac-Minh Thai

Int. J. Mol. Sci. 2022, 23(24), 16083; https://doi.org/10.3390/ijms232416083 - 16 Dec 2022

Viewed by 2804

Abstract

Antibiotic resistance has been becoming more and more critical due to bacteria’s evolving hydrolysis enzymes. The NDM-1 enzyme could hydrolyze not only carbapenems but also most of β-lactam’s antibiotics and inhibitors. In fact, variant strains could impose a high impact on the resistance [...] Read more.

Antibiotic resistance has been becoming more and more critical due to bacteria’s evolving hydrolysis enzymes. The NDM-1 enzyme could hydrolyze not only carbapenems but also most of β-lactam’s antibiotics and inhibitors. In fact, variant strains could impose a high impact on the resistance of bacteria producing NDM-1. Although previous studies showed the effect of some variants toward antibiotics and inhibitors binding, there has been no research systematically evaluating the effects of alternative one-point mutations on the hydrolysis capacity of NDM-1. This study aims to identify which mutants could increase or decrease the effectiveness of antibiotics and β-lactamase inhibitors toward bacteria. Firstly, 35 different variants with a high probability of emergence based on the PAM-1 matrix were constructed and then docked with 5 ligands, namely d-captopril, l-captopril, thiorphan, imipenem, and meropenem. The selected complexes underwent molecular dynamics simulation and free energy binding estimation, with the results showing that the substitutions at residues 122 and 124 most influenced the binding ability of NDM-1 toward inhibitors and antibiotics. The H122R mutant decreases the binding ability between d-captopril and NDM-1 and diminishes the effectiveness of this antibiotic toward Enterobacteriaceae. However, the H122R mutant has a contrary impact on thiorphan, which should be tested in vitro and in vivo in further experiments. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

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15 pages, 24209 KiB

Open AccessArticle

Computational Prediction of Resistance Induced Alanine-Mutation in ATP Site of Epidermal Growth Factor Receptor

by Tasia Amelia, Aderian Novito Setiawan, Rahmana Emran Kartasasmita, Tomohiko Ohwada and Daryono Hadi Tjahjono

Int. J. Mol. Sci. 2022, 23(24), 15828; https://doi.org/10.3390/ijms232415828 - 13 Dec 2022

Cited by 3 | Viewed by 1483

Abstract

Epidermal growth factor receptor (EGFR) resistance to tyrosine kinase inhibitors can cause low survival rates in mutation-positive non-small cell lung cancer patients. It is necessary to predict new mutations in the development of more potent EGFR inhibitors since classical and rare mutations observed [...] Read more.

Epidermal growth factor receptor (EGFR) resistance to tyrosine kinase inhibitors can cause low survival rates in mutation-positive non-small cell lung cancer patients. It is necessary to predict new mutations in the development of more potent EGFR inhibitors since classical and rare mutations observed were known to affect the effectiveness of the therapy. Therefore, this research aimed to perform alanine mutagenesis scanning on ATP binding site residues without COSMIC data, followed by molecular dynamic simulations to determine their molecular interactions with ATP and erlotinib compared to wild-type complexes. Based on the result, eight mutations were found to cause changes in the binding energy of the ATP analogue to become more negative. These included G779A, Q791A, L792A, R841A, N842A, V843A, I853A, and D855A, which were predicted to enhance the affinity of ATP and reduce the binding ability of inhibitors with the same interaction site. Erlotinib showed more positive energy among G779A, Q791A, I853A, and D855A, due to their weaker binding energy than ATP. These four mutations could be anticipated in the development of the next inhibitor to overcome the incidence of resistance in lung cancer patients. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

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34 pages, 47553 KiB

Open AccessArticle

Hierarchical Coarse-Grained Strategy for Macromolecular Self-Assembly: Application to Hepatitis B Virus-Like Particles

by Philipp Nicolas Depta, Maksym Dosta, Wolfgang Wenzel, Mariana Kozlowska and Stefan Heinrich

Int. J. Mol. Sci. 2022, 23(23), 14699; https://doi.org/10.3390/ijms232314699 - 24 Nov 2022

Cited by 2 | Viewed by 2311

Abstract

Macromolecular self-assembly is at the basis of many phenomena in material and life sciences that find diverse applications in technology. One example is the formation of virus-like particles (VLPs) that act as stable empty capsids used for drug delivery or vaccine fabrication. Similarly [...] Read more.

Macromolecular self-assembly is at the basis of many phenomena in material and life sciences that find diverse applications in technology. One example is the formation of virus-like particles (VLPs) that act as stable empty capsids used for drug delivery or vaccine fabrication. Similarly to the capsid of a virus, VLPs are protein assemblies, but their structural formation, stability, and properties are not fully understood, especially as a function of the protein modifications. In this work, we present a data-driven modeling approach for capturing macromolecular self-assembly on scales beyond traditional molecular dynamics (MD), while preserving the chemical specificity. Each macromolecule is abstracted as an anisotropic object and high-dimensional models are formulated to describe interactions between molecules and with the solvent. For this, data-driven protein–protein interaction potentials are derived using a Kriging-based strategy, built on high-throughput MD simulations. Semi-automatic supervised learning is employed in a high performance computing environment and the resulting specialized force-fields enable a significant speed-up to the micrometer and millisecond scale, while maintaining high intermolecular detail. The reported generic framework is applied for the first time to capture the formation of hepatitis B VLPs from the smallest building unit, i.e., the dimer of the core protein HBcAg. Assembly pathways and kinetics are analyzed and compared to the available experimental observations. We demonstrate that VLP self-assembly phenomena and dependencies are now possible to be simulated. The method developed can be used for the parameterization of other macromolecules, enabling a molecular understanding of processes impossible to be attained with other theoretical models. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

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16 pages, 3075 KiB

Open AccessArticle

Cooling-Rate Computer Simulations for the Description of Crystallization of Organic Phase-Change Materials

by Victor M. Nazarychev, Artyom D. Glova, Sergey V. Larin, Alexey V. Lyulin, Sergey V. Lyulin and Andrey A. Gurtovenko

Int. J. Mol. Sci. 2022, 23(23), 14576; https://doi.org/10.3390/ijms232314576 - 23 Nov 2022

Cited by 6 | Viewed by 2068

Abstract

A molecular-level insight into phase transformations is in great demand for many molecular systems. It can be gained through computer simulations in which cooling is applied to a system at a constant rate. However, the impact of the cooling rate on the crystallization [...] Read more.

A molecular-level insight into phase transformations is in great demand for many molecular systems. It can be gained through computer simulations in which cooling is applied to a system at a constant rate. However, the impact of the cooling rate on the crystallization process is largely unknown. To this end, here we performed atomic-scale molecular dynamics simulations of organic phase-change materials (paraffins), in which the cooling rate was varied over four orders of magnitude. Our computational results clearly show that a certain threshold (1.2 × 10¹¹ K/min) in the values of cooling rates exists. When cooling is slower than the threshold, the simulations qualitatively reproduce an experimentally observed abrupt change in the temperature dependence of the density, enthalpy, and thermal conductivity of paraffins upon crystallization. Beyond this threshold, when cooling is too fast, the paraffin’s properties in simulations start to deviate considerably from experimental data: the faster the cooling, the larger part of the system is trapped in the supercooled liquid state. Thus, a proper choice of a cooling rate is of tremendous importance in computer simulations of organic phase-change materials, which are of great promise for use in domestic heat storage devices. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

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20 pages, 17103 KiB

Open AccessArticle

Chalcogen Bond as a Factor Stabilizing Ligand Conformation in the Binding Pocket of Carbonic Anhydrase IX Receptor Mimic

by Kamil Wojtkowiak, Mariusz Michalczyk, Wiktor Zierkiewicz, Aneta Jezierska and Jarosław J. Panek

Int. J. Mol. Sci. 2022, 23(22), 13701; https://doi.org/10.3390/ijms232213701 - 08 Nov 2022

Cited by 8 | Viewed by 1301

Abstract

It is postulated that the overexpression of Carbonic Anhydrase isozyme IX in some cancers contributes to the acidification of the extracellular matrix. It was proved that this promotes the growth and metastasis of the tumor. These observations have made Carbonic Anhydrase IX an [...] Read more.

It is postulated that the overexpression of Carbonic Anhydrase isozyme IX in some cancers contributes to the acidification of the extracellular matrix. It was proved that this promotes the growth and metastasis of the tumor. These observations have made Carbonic Anhydrase IX an attractive drug target. In the light of the findings and importance of the glycoprotein in the cancer treatment, we have employed quantum–chemical approaches to study non-covalent interactions in the binding pocket. As a ligand, the acetazolamide (AZM) molecule was chosen, being known as a potential inhibitor exhibiting anticancer properties. First-Principles Molecular Dynamics was performed to study the chalcogen and other non-covalent interactions in the AZM ligand and its complexes with amino acids forming the binding site. Based on Density Functional Theory (DFT) and post-Hartree–Fock methods, the metric and electronic structure parameters were described. The Non-Covalent Interaction (NCI) index and Atoms in Molecules (AIM) methods were applied for qualitative/quantitative analyses of the non-covalent interactions. Finally, the AZM–binding pocket interaction energy decomposition was carried out. Chalcogen bonding in the AZM molecule is an important factor stabilizing the preferred conformation. Free energy mapping via metadynamics and Path Integral molecular dynamics confirmed the significance of the chalcogen bond in structuring the conformational flexibility of the systems. The developed models are useful in the design of new inhibitors with desired pharmacological properties. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

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19 pages, 6893 KiB

Open AccessArticle

Acetophenone-Based 3,4-Dihydropyrimidine-2(1H)-Thione as Potential Inhibitor of Tyrosinase and Ribonucleotide Reductase: Facile Synthesis, Crystal Structure, In-Vitro and In-Silico Investigations

by Aamer Saeed, Syeda Abida Ejaz, Aqsa Khalid, Pervaiz Ali Channar, Mubashir Aziz, Qamar Abbas, Tanveer A. Wani, Nawaf A. Alsaif, Mohammed M. Alanazi, Abdullah M. Al-Hossaini, Nojood Altwaijry, Seema Zargar, Muawya Elhadi and Tuncer Hökelek

Int. J. Mol. Sci. 2022, 23(21), 13164; https://doi.org/10.3390/ijms232113164 - 29 Oct 2022

Cited by 6 | Viewed by 1737

Abstract

The acetophenone-based 3,4-dihydropyrimidine-2(1H)-thione was synthesized by the reaction of 4-methylpent-3-en-2-one (1), 4-acetyl aniline (2) and potassium thiocyanate. The spectroscopic analysis including: FTIR, ¹H-NMR, and single crystal analysis proved the structure of synthesized compound (4), with the [...] Read more.

The acetophenone-based 3,4-dihydropyrimidine-2(1H)-thione was synthesized by the reaction of 4-methylpent-3-en-2-one (1), 4-acetyl aniline (2) and potassium thiocyanate. The spectroscopic analysis including: FTIR, ¹H-NMR, and single crystal analysis proved the structure of synthesized compound (4), with the six-membered nonplanar ring in envelope conformation. In crystal structure, the intermolecular N–H ⋯ S and C–H ⋯ O hydrogen bonds link the molecule in a two-dimensional manner which is parallel to (010) the plane enclosing R₂² (8) and R₂² (10) ring motifs. After that, the Hirshfeld surfaces and their related two-dimensional fingerprint plots were used for thorough investigation of intermolecular interactions. According to Hirshfeld surface analysis, the most substantial contributions to the crystal packing are from H ⋯ H (59.5%), H ⋯ S/S ⋯ H (16.1%), and H ⋯ C/C ⋯ H (13.1%) interactions. The electronic properties and stability of the compound were investigated through density functional theory (DFT) studies using B3LYP functional and 6-31G* as a basis set. The compound 4 displayed the high chemical reactivity with chemical softness of 2.48. In comparison to the already reported known tyrosinase inhibitor, the newly synthesized derivatives exhibited almost seven-fold better inhibition of tyrosinase (IC₅₀ = 1.97 μM), which was further supported by molecular docking studies. The compound 4 inside the active pocket of ribonucleotide reductase (RNR) exhibited a binding energy of −19.68 kJ/mol, and with mammalian deoxy ribonucleic acid (DNA) it acts as an effective DNA groove binder with a binding energy of −21.32 kJ/mol. The results suggested further exploration of this compound at molecular level to synthesize more potential leads for the treatment of cancer. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

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14 pages, 5690 KiB

Open AccessArticle

Observing How Glutathione and S-Hexyl Glutathione Bind to Glutathione S-Transferase from Rhipicephalus (Boophilus) microplus

by Warin Rangubpit, Eukote Suwan, Danai Sangthong, Kannika Wongpanit, Roger W. Stich, Prapasiri Pongprayoon and Sathaporn Jittapalapong

Int. J. Mol. Sci. 2022, 23(21), 12775; https://doi.org/10.3390/ijms232112775 - 23 Oct 2022

Cited by 2 | Viewed by 1753

Abstract

Rhipicephalus (Boophilus) microplus is one of the most widespread ticks causing a massive loss to livestock production. The long-term use of acaracides rapidly develops acaracide resistance. In R. microplus, enhancing the metabolic activity of glutathione S-transferase (RmGST) is one of the mechanisms [...] Read more.

Rhipicephalus (Boophilus) microplus is one of the most widespread ticks causing a massive loss to livestock production. The long-term use of acaracides rapidly develops acaracide resistance. In R. microplus, enhancing the metabolic activity of glutathione S-transferase (RmGST) is one of the mechanisms underlying acaracide resistance. RmGST catalyzes the conjugation of glutathione (GSH) to insecticides causing an easy-to-excrete conjugate. The active RmGST dimer contains two active sites (hydrophobic co-substrate binding site (H-site) and GSH binding site (G-site)) in each monomer. To preserve the insecticide efficacy, s-hexyl glutathione (GTX), a GST inhibitor, has been used as a synergist. To date, no molecular information on the RmGST-GSH/GTX complex is available. The insight is important for developing a novel RmGST inhibitor. Therefore, in this work, molecular dynamics simulations (MD) were performed to explore the binding of GTX and GSH to RmGST. GSH binds tighter and sits rigidly inside the G-site, while flexible GTX occupies both active sites. In GSH, the backbone mainly interacts with W8, R43, W46, K50, N59, L60, Q72, and S73, while its thiol group directs to Y7. In contrast, the aliphatic hexyl of GTX protrudes into the H-site and allows a flexible peptide core to form various interactions. Such high GTX flexibility and the protrusion of its hexyl moiety to the H-site suggest the dual role of GTX in preventing the conjugation reaction and the binding of acaracide. This insight can provide a better understanding of an important insecticide-resistance mechanism, which may in turn facilitate the development of novel approaches to tick control. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

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18 pages, 5815 KiB

Open AccessArticle

H₂, CO₂, and CH₄ Adsorption Potential of Kerogen as a Function of Pressure, Temperature, and Maturity

by Arshad Raza, Mohamed Mahmoud, Saad Alafnan, Muhammad Arif and Guenther Glatz

Int. J. Mol. Sci. 2022, 23(21), 12767; https://doi.org/10.3390/ijms232112767 - 23 Oct 2022

Cited by 17 | Viewed by 2138

Abstract

We performed molecular dynamics simulation to elucidate the adsorption behavior of hydrogen (H₂), carbon dioxide (CO₂), and methane (CH₄) on four sub-models of type II kerogens (organic matter) of varying thermal maturities over a wide range of [...] Read more.

We performed molecular dynamics simulation to elucidate the adsorption behavior of hydrogen (H₂), carbon dioxide (CO₂), and methane (CH₄) on four sub-models of type II kerogens (organic matter) of varying thermal maturities over a wide range of pressures (2.75 to 20 MPa) and temperatures (323 to 423 K). The adsorption capacity was directly correlated with pressure but indirectly correlated with temperature, regardless of the kerogen or gas type. The maximum adsorption capacity was 10.6 mmol/g for the CO₂, 7.5 mmol/g for CH₄, and 3.7 mmol/g for the H₂ in overmature kerogen at 20 MPa and 323 K. In all kerogens, adsorption followed the trend CO₂ > CH₄ > H₂ attributed to the larger molecular size of CO₂, which increased its affinity toward the kerogen. In addition, the adsorption capacity was directly associated with maturity and carbon content. This behavior can be attributed to a specific functional group, i.e., H, O, N, or S, and an increase in the effective pore volume, as both are correlated with organic matter maturity, which is directly proportional to the adsorption capacity. With the increase in carbon content from 40% to 80%, the adsorption capacity increased from 2.4 to 3.0 mmol/g for H₂, 7.7 to 9.5 mmol/g for CO₂, and 4.7 to 6.3 mmol/g for CH₄ at 15 MPa and 323 K. With the increase in micropores, the porosity increased, and thus II-D offered the maximum adsorption capacity and the minimum II-A kerogen. For example, at a fixed pressure (20 MPa) and temperature (373 K), the CO₂ adsorption capacity for type II-A kerogen was 7.3 mmol/g, while type II-D adsorbed 8.9 mmol/g at the same conditions. Kerogen porosity and the respective adsorption capacities of all gases followed the order II-D > II-C > II-B > II-A, suggesting a direct correlation between the adsorption capacity and kerogen porosity. These findings thus serve as a preliminary dataset on the gas adsorption affinity of the organic-rich shale reservoirs and have potential implications for CO₂ and H₂ storage in organic-rich formations. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

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16 pages, 4809 KiB

Open AccessArticle

Conformational Heterogeneity and Frustration of the Tumor Suppressor p53 as Tuned by Punctual Mutations

by Anna Rita Bizzarri

Int. J. Mol. Sci. 2022, 23(20), 12636; https://doi.org/10.3390/ijms232012636 - 20 Oct 2022

Viewed by 1310

Abstract

The conformational heterogeneity of the p53 tumor suppressor, the wild-type (p53wt) and mutated forms, was investigated by a computational approach, including the modeling and all atoms of the molecular dynamics (MD) simulations. Four different punctual mutations (p53R175H, p53R248Q, p53R273H, and p53R282W) which are [...] Read more.

The conformational heterogeneity of the p53 tumor suppressor, the wild-type (p53wt) and mutated forms, was investigated by a computational approach, including the modeling and all atoms of the molecular dynamics (MD) simulations. Four different punctual mutations (p53R175H, p53R248Q, p53R273H, and p53R282W) which are known to affect the DNA binding and belong to the most frequent hot-spot mutations in human cancers, were taken into consideration. The MD trajectories of the wild-type and mutated p53 forms were analyzed by essential dynamics to extract the relevant collective motions and by the frustration method to evaluate the degeneracy of the energy landscape. We found that p53 is characterized by wide collective motions and its energy landscape exhibits a rather high frustration level, especially in the regions involved in the binding to physiological ligands. Punctual mutations give rise to a modulation of both the collective motions and the frustration of p53, with different effects depending on the mutation. The regions of p53wt and of the mutated forms characterized by a high frustration level are also largely involved in the collective motions. Such a correlation is discussed also in connection with the intrinsic disordered character of p53 and with its central functional role. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

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17 pages, 7035 KiB

Open AccessArticle

Analysis of 1-Aroyl-3-[3-chloro-2-methylphenyl] Thiourea Hybrids as Potent Urease Inhibitors: Synthesis, Biochemical Evaluation and Computational Approach

by Samina Rasheed, Mubashir Aziz, Aamer Saeed, Syeda Abida Ejaz, Pervaiz Ali Channar, Seema Zargar, Qamar Abbas, Humidah Alanazi, Mumtaz Hussain, Mona Alharbi, Song Ja Kim, Tanveer A. Wani and Hussain Raza

Int. J. Mol. Sci. 2022, 23(19), 11646; https://doi.org/10.3390/ijms231911646 - 01 Oct 2022

Cited by 12 | Viewed by 1702

Abstract

Urease is an amidohydrolase enzyme that is responsible for fatal morbidities in the human body, such as catheter encrustation, encephalopathy, peptic ulcers, hepatic coma, kidney stone formation, and many others. In recent years, scientists have devoted considerable efforts to the quest for efficient [...] Read more.

Urease is an amidohydrolase enzyme that is responsible for fatal morbidities in the human body, such as catheter encrustation, encephalopathy, peptic ulcers, hepatic coma, kidney stone formation, and many others. In recent years, scientists have devoted considerable efforts to the quest for efficient urease inhibitors. In the pharmaceutical chemistry, the thiourea skeleton plays a vital role. Thus, the present work focused on the development and discovery of novel urease inhibitors and reported the synthesis of a set of 1-aroyl-3-[3-chloro-2-methylphenyl] thiourea hybrids with aliphatic and aromatic side chains 4a–j. The compounds were characterized by different analytical techniques including FT-IR, ¹H-NMR, and ¹³C-NMR, and were evaluated for in-vitro enzyme inhibitory activity against jack bean urease (JBU), where they were found to be potent anti-urease inhibitors and the inhibitory activity IC₅₀ was found in the range of 0.0019 ± 0.0011 to 0.0532 ± 0.9951 μM as compared to the standard thiourea (IC₅₀ = 4.7455 ± 0.0545 μM). Other studies included density functional theory (DFT), antioxidant radical scavenging assay, physicochemical properties (ADMET properties), molecular docking and molecular dynamics simulations. All compounds were found to be more active than the standard, with compound 4i exhibiting the greatest JBU enzyme inhibition (IC₅₀ value of 0.0019 ± 0.0011 µM). The kinetics of enzyme inhibition revealed that compound 4i exhibited non-competitive inhibition with a Ki value of 0.0003 µM. The correlation between DFT experiments with a modest HOMO-LUMO energy gap and biological data was optimal. These recently identified urease enzyme inhibitors may serve as a starting point for future research and development. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

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15 pages, 5008 KiB

Open AccessArticle

Cloning and Characterization of Fructose-1,6-Bisphosphate Aldolase from Euphausia superba

by Jikun Xia, Wanmeng Xin, Fang Wang, Wancui Xie, Yi Liu and Jiakun Xu

Int. J. Mol. Sci. 2022, 23(18), 10478; https://doi.org/10.3390/ijms231810478 - 09 Sep 2022

Cited by 3 | Viewed by 2561

Abstract

Fructose-1,6-bisphosphate aldolase (EC 4.1.2.13) is a highly conserved enzyme that is involved in glycolysis and gluconeogenesis. In this study, we cloned the fructose-1,6-bisphosphate aldolase gene from Euphausia superba (EsFBA). The full-length cDNA sequence of EsFBA is 1098 bp long and encodes a 365-amino-acid [...] Read more.

Fructose-1,6-bisphosphate aldolase (EC 4.1.2.13) is a highly conserved enzyme that is involved in glycolysis and gluconeogenesis. In this study, we cloned the fructose-1,6-bisphosphate aldolase gene from Euphausia superba (EsFBA). The full-length cDNA sequence of EsFBA is 1098 bp long and encodes a 365-amino-acid protein. The fructose-1,6-bisphosphate aldolase gene was expressed in Escherichia coli (E. coli). A highly purified protein was obtained using HisTrap HP affinity chromatography and size-exclusion chromatography. The predicted three-dimensional structure of EsFBA showed a 65.66% homology with human aldolase, whereas it had the highest homology (84.38%) with the FBA of Penaeus vannamei. Recombinant EsFBA had the highest activity at 45 °C and pH 7.0 in phosphate buffer. By examining the activity of metal ions and EDTA, we found that the effect of metal ions and EDTA on EsFBA’s enzyme activity was not significant, while the presence of borohydride severely reduced the enzymatic activity; thus, EsFBA was confirmed to be a class I aldolase. Furthermore, targeted mutations at positions 34, 147, 188, and 230 confirmed that they are key amino acid residues for EsFBA. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

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12 pages, 8479 KiB

Open AccessArticle

Theoretical Design of a Janus-Nanoparticle-Based Sandwich Assay for Nucleic Acids

by Takumi Sato, Keiko Esashika, Eiji Yamamoto, Toshiharu Saiki and Noriyoshi Arai

Int. J. Mol. Sci. 2022, 23(15), 8807; https://doi.org/10.3390/ijms23158807 - 08 Aug 2022

Cited by 1 | Viewed by 1614

Abstract

Nanoparticles exhibit diverse self-assembly attributes and are expected to be applicable under unique settings. For instance, biomolecules can be sandwiched between dimer nanoparticles and detected by surface-enhanced Raman scattering. Controlling the gap between extremely close dimers and stably capturing the target molecule in [...] Read more.

Nanoparticles exhibit diverse self-assembly attributes and are expected to be applicable under unique settings. For instance, biomolecules can be sandwiched between dimer nanoparticles and detected by surface-enhanced Raman scattering. Controlling the gap between extremely close dimers and stably capturing the target molecule in the gap are crucial aspects of this strategy. Therefore, polymer-tethered nanoparticles (PTNPs), which show promise as high-performance materials that exhibit the attractive features of both NPs and polymers, were targeted in this study to achieve stable biomolecule sensing. Using coarse-grained molecular dynamics simulations, the dependence of the PTNP interactions on the length of the grafted polymer, graft density, and coverage ratio of a hydrophobic tether were examined. The results indicated that the smaller the tether length and graft density, the smaller was the distance between the PTNP surfaces (

R_{surf}

). In contrast,

R_{surf}

decreased as the coverage ratio of the hydrophobic surface (

ϕ

) increased. The sandwiching probability of the sensing target increased in proportion to the coverage ratio. At high

ϕ

values, the PTNPs aggregated into three or more particles, which hindered their sensing attributes. These results provide fundamental insight into the sensing applications of NPs and demonstrate the usefulness of PTNPs in sensing biomolecules. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

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20 pages, 12667 KiB

Open AccessArticle

Shape Transformations and Self-Assembly of Hairy Particles under Confinement

by Małgorzata Borówko and Tomasz Staszewski

Int. J. Mol. Sci. 2022, 23(14), 7919; https://doi.org/10.3390/ijms23147919 - 18 Jul 2022

Cited by 4 | Viewed by 1770

Abstract

Molecular dynamics simulations are used to investigate the behavior of polymer-tethered nanoparticles between two inert or attractive walls. The confinement in pores creates new possibilities for controlling the shape transformation of individual hairy particles and their self-organization. We introduce a minimalistic model of [...] Read more.

Molecular dynamics simulations are used to investigate the behavior of polymer-tethered nanoparticles between two inert or attractive walls. The confinement in pores creates new possibilities for controlling the shape transformation of individual hairy particles and their self-organization. We introduce a minimalistic model of the system; only chain-wall interactions are assumed to be attractive, while the others are softly repulsive. We show how the shape of isolated particles can be controlled by changing the wall separation and the strength of the interaction with the surfaces. For attractive walls, we found two types of structures, “bridges” and “mounds”. The first structures are similar to flanged spools in which the chains are connected with both walls and form bridges between them. We observed various bridges, symmetrical and asymmetrical spools, hourglasses, and pillars. The bridge-like structures can be “nano-oscillators” in which the cores jump from one wall to the other. We also study the self-assembly of a dense fluid of hairy particles in slit-like pores and analyze how the system morphology depends on interactions with the surfaces and the wall separation. The hairy particles form layers parallel to the walls. Different ordered structures, resembling two-dimensional crystalline lattices, are reported. We demonstrate that hairy particles are a versatile soft component forming a variety of structures in the slits. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

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20 pages, 2651 KiB

Open AccessArticle

Archaeal Lipids Regulating the Trimeric Structure Dynamics of Bacteriorhodopsin for Efficient Proton Release and Uptake

by Sijin Chen, Xiaoyan Ding, Chao Sun, Fei Wang, Xiao He, Anthony Watts and Xin Zhao

Int. J. Mol. Sci. 2022, 23(13), 6913; https://doi.org/10.3390/ijms23136913 - 21 Jun 2022

Cited by 4 | Viewed by 1834

Abstract

S-TGA-1 and PGP-Me are native archaeal lipids associated with the bacteriorhodopsin (bR) trimer and contribute to protein stabilization and native dynamics for proton transfer. However, little is known about the underlying molecular mechanism of how these lipids regulate bR trimerization and efficient photocycling. [...] Read more.

S-TGA-1 and PGP-Me are native archaeal lipids associated with the bacteriorhodopsin (bR) trimer and contribute to protein stabilization and native dynamics for proton transfer. However, little is known about the underlying molecular mechanism of how these lipids regulate bR trimerization and efficient photocycling. Here, we explored the specific binding of S-TGA-1 and PGP-Me with the bR trimer and elucidated how specific interactions modulate the bR trimeric structure and proton release and uptake using long-term atomistic molecular dynamic simulations. Our results showed that S-TGA-1 and PGP-Me are essential for stabilizing the bR trimer and maintaining the coherent conformational dynamics necessary for proton transfer. The specific binding of S-TGA-1 with W80 and K129 regulates proton release on the extracellular surface by forming a “Glu-shared” model. The interaction of PGP-Me with K40 ensures proton uptake by accommodating the conformation of the helices to recruit enough water molecules on the cytoplasmic side. The present study results could fill in the theoretical gaps of studies on the functional role of archaeal lipids and could provide a reference for other membrane proteins containing similar archaeal lipids. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

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12 pages, 5108 KiB

Open AccessArticle

Dynamics of Ultrafast Phase Transitions in (001) Si on the Shock-Wave Front

by Evgenii Igorevich Mareev and Fedor Viktorovich Potemkin

Int. J. Mol. Sci. 2022, 23(4), 2115; https://doi.org/10.3390/ijms23042115 - 14 Feb 2022

Cited by 3 | Viewed by 1626

Abstract

We demonstrate an ultrafast (<0.1 ps) reversible phase transition in silicon (Si) under ultrafast pressure loading using molecular dynamics. Si changes its structure from cubic diamond to β-Sn on the shock-wave front. The phase transition occurs when the shock-wave pressure exceeds 11 GPa. [...] Read more.

We demonstrate an ultrafast (<0.1 ps) reversible phase transition in silicon (Si) under ultrafast pressure loading using molecular dynamics. Si changes its structure from cubic diamond to β-Sn on the shock-wave front. The phase transition occurs when the shock-wave pressure exceeds 11 GPa. Atomic volume, centrosymmetry, and the X-ray-diffraction spectrum were revealed as effective indicators of phase-transition dynamics. The latter, being registered in actual experimental conditions, constitutes a breakthrough in the path towards simple X-ray optical cross-correlation and pump-probe experiments. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

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