Van Der Waals Energy Research Articles

<i>In silico</i> Screening of Chemical Constituents in <i>Rasam</i> as a Beneficial Supplementary Treatment for Novel Coronavirus

<strong>Context:</strong> The novel coronavirus named as COVID-19 (SARS-CoV-2) from its origin in Hubei spread across the continent in a short period of six months’ time. Till date there is no drug to cure the novel corona virus SARS-CoV-2. Earlier studies on SARS-CoV-1 suggests that interleukin 6 (IL-6) and Interleukin 8 (IL-8) were in the higher levels indicating the key role of IL. <strong>Aim:</strong> Molecular simulation studies were carried out on the selected 24 chemical constituents present in rasam against IL-6 to identify the key interaction between the amino acid residues and their chemical structure. <strong>Materials and Methods:</strong> A library of 24 chemical constituents was sketched using Chem Sketch programming 8.0. The 3D structures of ligands were retrieved in mol format in Maestro v 11.3 and the ligands were optimized utilizing ligprep (4.3) module (Schrödinger 2018-1). <strong>Results:</strong> One of the chemical constituents sinigrin a glucosinolate emerged as top scorer with a GLIDE score of -6.333. It was apparent from the examination, that the Van der Waals (ΔG bindvdW) and coulomb energy interactions were major great contributors. The structural diversity of sinigrin from the rest of other chemical constituents in rasam led to significantly better interaction with amino acid residues. <strong>Conclusion:</strong> The study identifies sinigrin, as one of the active constituents in rasam possessing good binding affinity against IL-6 which can be used as a dietary supplement and can be used as a control measure to fight against Covid-19.

A novel multi-objective metaheuristic algorithm for protein-peptide docking and benchmarking on the LEADS-PEP dataset

Protein-peptide interactions have attracted the attention of many drug discovery scientists due to their possible druggability features on most key biological activities such as regulating disease-related signaling pathways and enhancing the immune system's responses. Different studies have utilized some protein-peptide-specific docking algorithms/methods to predict protein-peptide interactions. However, the existing algorithms/methods suffer from two serious limitations which make them unsuitable for protein-peptide docking problems. First, it seems that the prevalent approaches require to be modified and remodeled for weighting the unbounded forces between a protein and a peptide. Second, they do not employ state-of-the-art search algorithms for detecting the 3D pose of a peptide relative to a protein. To address these restrictions, the present study aims to introduce a novel multi-objective algorithm, which first generates some potential 3D poses of a peptide, and then, improves them through its operators. The candidate solutions are further evaluated using Multi-Objective Pareto Front (MOPF) optimization concepts. To this end, van der Waals, electrostatic, solvation, and hydrogen bond energies between the atoms of a protein and designated peptide are computed. To evaluate the algorithm, it is first applied to the LEADS-PEP dataset containing 53 protein-peptide complexes with up to 53 rotatable branches/bonds and then compared with three popular/efficient algorithms. The obtained results indicate that the MOPF-based approaches which reduce the backbone RMSD between the original and predicted states, achieve significantly better results in terms of the success rate in predicting the near-native conditions. Besides, a comparison between the different types of search algorithms reveals that efficient ones like the multi-objective Trader/differential evolution algorithm can predict protein-peptide interactions better than the popular algorithms such as the multi-objective genetic/particle swarm optimization algorithms.

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

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.

Adsorption, stability and evolution path of benzene on graphene surface: Size and edge effects

Compared with other drug carriers, graphene materials attract more attention due to their large specific surface area, strong targeting and controlled release. Graphene adsorbs anticancer drugs such as doxorubicin and paclitaxel via strong π-π interaction between graphene and the aromatic conjugated structure in drug molecules. The adsorptionstability of benzene as minimum aromatic conjugated structure on graphene surface is investigated in this research. The evolution paths of relative stable and unstable positions strongly depend on the size of graphene. For graphene with different size ratios, the evolution paths of benzene go through different stages with decrease of adsorption height and the most stable adsorption position can be found. Based on the interaction energy, the edge effect of graphene with finite size is used to reveal the mechanism of size effect, which is caused by the competition between van der Waals energy and electrostatic energy. This research can provide a reference for the manufacture and application of graphene as drug carriers.

Molecular Docking and Simulation Studies of Antidiabetic Agents Devised from Hypoglycemic Polypeptide-P of Momordica charantia.

Diabetes mellitus termed as metabolic disorder is a collection of interlinked diseases and mainly body's inability to manage glucose level which leads to cardiovascular diseases, renal failure, neurological disorders, and many others. The drugs contemporarily used for diabetes have many inevitable side effects, and many of them have become less responsive to this multifactorial disorder. Momordica charantia commonly known as bitter gourd has many bioactive compounds with antidiabetic properties. The current study was designed to use computational methods to discover the best antidiabetic peptides devised from hypoglycemic polypeptide-P of M. charantia. The binding affinity and interaction patterns of peptides were evaluated against four receptor proteins (i.e., as agonists of insulin receptor and inhibitors of sodium-glucose cotransporter 1, dipeptidyl peptidase-IV, and glucose transporter 2) using molecular docking approach. A total of thirty-seven peptides were docked against these receptors. Out of which, top five peptides against each receptor were shortlisted based on their S-scores and binding affinities. Finally, the eight best ligands (i.e., LIVA, TSEP, EKAI, LKHA, EALF, VAEK, DFGAS, and EPGGGG) were selected as these ligands strictly followed Lipinski's rule of five and exhibited good ADMET profiling. One peptide EPGGGG showed activity towards insulin and SGLT1 receptor proteins. The top complex for both these targets was subjected to 50 ns of molecular dynamics simulations and MM-GBSA binding energy test that concluded both complexes as highly stable, and the intermolecular interactions were dominated by van der Waals and electrostatic energies. Overall, the selected ligands strongly fulfilled the drug-like evaluation criterion and proved to have good antidiabetic properties.

Bionanoscale Recognition Underlies Cell Fate and Therapy.

Understanding the bionanoscale recognition of nanostructured architectures is critical to the design and application of nanomaterials, but the related information is not well understood. In this study, it is found that bionanoscale recognition underlies cell fate and therapy. For example, 1T phase (octahedral coordination) monolayer MoS2 exhibits a markedly stronger affinity for fibronectin than the 2H structure (triangular prism coordination) and promotes cell spreading and differentiation. The van der Waals energy and increased turn components contribute to the high adhesion of fibronectin onto the 1T-MoS2 structure. 1T-MoS2 exhibits a significantly stronger affinity (KD , 6.59× 10-7 m) for liposomes than 2H-MoS2 (1.21× 10-6 m) due to strong hydrophobic interactions. The existence of octahedrally coordinated atomic structures that improve cell viability by enhancing the neurite length is first proven by random forest and structural equation models. Consequently, octahedral coordination disaggregates α-synuclein (e.g., by decreasing β-sheets and increasing coil structures) and protects cells and hosts against Parkinson's disease. As a proof-of-principle demonstration, these findings indicate that bionanoscale recognition underlies the design of biomaterials and cell therapeutics.

Unravelling the Mechanistic Role of Quinazolinone Pharmacophore in the Inhibitory Activity of Bis-quinazolinone Derivative on Tankyrase-1 in the Treatment of Colorectal Cancer (CRC) and Non-small Cell Lung Cancer (NSCLC): A Computational Approach.

In recent years, tankyrase inhibition has gained a great focus as an anti-cancer strategy due to their modulatory effect on WNT/β-catenin pathway implicated in many malignancies, including colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). Based on the structural homology in the catalytic domain of PARP enzymes, bis-quinazolinone 5 (Cpd 5) was designed to be a potent selective tankyrase inhibitor. In this study, we employed molecular dynamics simulations and binding energy analysis to decipher the underlying mechanism of TNK-1 inhibition by Cpd 5 in comparison with a known selective tankyrase, IWR-1. The Cpd 5 had a relatively higher ΔGbind than IWR-1 from the thermodynamics analysis, revealing the better inhibitory activity of Cpd 5 compared to IWR-1. High involvement of solvation energy (ΔGsol) and the van der Waals energy (ΔEvdW) potentiated the affinity of Cpd 5 at TNK-1 active site. Interestingly, the keto group and the N3 atom of the quinazolinone nucleus of Cpd 5, occupying the NAM subsite, was able to form H-bond with Gly1185, thereby favoring the better stability and higher inhibitory efficacy of Cpd 5 relative to IWR-1. Our analysis proved that the firm binding of Cpd 5 was achieved by the quinazolinone groups via the hydrophobic interactions with the side chains of key site residues at the two subsite regions: His1201, Phe1188, Ala1191, and Ile1192 at the AD subsite and Tyr1224, Tyr1213, and Ala1215 at the NAM subsite. Thus, Cpd 5 is dominantly bound through π-π stacked interactions and other hydrophobic interactions. We believe that findings from this study would provide an important rationale towards the structure-based design of improved selective tankyrase inhibitors in cancer therapy.

Enantioseparation of mandelic acid and substituted derivatives by high-performance liquid chromatography with hydroxypropyl-β-cyclodextrin as chiral mobile additive and evaluation of inclusion complexes by molecular dynamics.

The enantioseparation and resolution mechanism of mandelic acid (MA), 4-methoxymandelic acid (MMA), and 4-propoxymandelic acid (PMA) were investigated by reversed-phase high-performance liquid chromatography (HPLC) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) as a chiral mobile-phase additive and molecular dynamics simulation. The suitable chromatographic conditions for the enantioseparation of MA, MMA, and PMA were obtained. Under the selected chromatographic conditions, these enantiomers could achieve baseline separation. The results of thermodynamic parameter analysis revealed that the main driven forces for the enantioseparation of MA, MMA, and PMA could be van der Waals forces and hydrogen-bonding interactions and the chromatographic retention of these chiral compounds was an enthalpy-driven process. The results of the molecular simulation revealed that their chiral resolution mechanism on HP-β-CD was responsible for the formation of inclusion complexes of enantiomers with HP-β-CD with different conformations and binding energies. And the binding energy of HP-β-CD with (S)-isomer was larger than that with (R)-isomer, which is consistent with the experimental results of the first elution of (S)-isomer. Additionally, it is also confirmed that the interaction energies included the van der Waals energy (∆Evdw ), electrostatic energy (∆Eelec ), polar solvation energy, and SASA energy (∆Esasa ), and the separation factor (α) was closely connected with the disparity in the binding energies of optical isomers and HP-β-CD complexes. Meanwhile, from molecular dynamics simulation, it can be found that the ∆(∆Ebinding ), (∆(∆Ebinding ) = ∆Ebinding,R - ∆Ebinding,S ) value was in order of MA-HP-β-CD complex > MMA-HP-β-CD complex > PMA-HP-β-CD complex, which was consistent with the order of Δ(ΔG) values obtained from van't Hoff plot. This indicated that the molecular dynamics simulation has predictive function for chiral resolution.

Mobility of solid and porous hollow SiO2 nanoparticles in saturated porous media: Impacts of surface and particle structure

Silica nanoparticles (SiO2 NPs) are of increasing interest in nano-enabled agriculture, particularly as nanocarriers for the targeted delivery of agrochemicals. Their direct application in agricultural soils may lead to the release of SiO2 NPs in the environment. Although some studies have investigated transport of solid SiO2 NPs in porous media, there is a knowledge gap on how different SiO2 NP structures incorporating significant porosities can affect the mobility of such particles under different conditions. Herein, we investigated the effect of pH and ionic strength (IS) on the transport of two distinct structures of SiO2 NPs, namely solid SiO2 NPs (SSNs) and porous hollow SiO2 NPs (PHSNs), of comparable sizes (~200 nm). Decreasing pH and increasing ionic strength reduced the mobility of PHSNs in sand-packed columns more significantly than for SSNs. The deposition of PHSNs was approximately 3 times greater than that of SSNs at pH 4.5 and IS 100 mM. The results are non-intuitive given that PHSNs have a lower density and the same chemical composition of SSNs but can be explained by the greater surface roughness and ten-fold greater specific surface area of PHSNs, and their impacts on van der Waals and electrostatic interaction energies.

Optoelectronic Synapses Based on Photo‐Induced Doping in MoS2/h‐BN Field‐Effect Transistors

AbstractSynaptic device is an important component in artificial neural networks. Electrically‐controlled long‐term depression (LTD) is demonstrated in three‐terminal photonic synaptic devices, which is useful for improving the efficiency of artificial neural networks. The mechanism of the three‐terminal photonic synaptic device is similar to that of the photo‐induced doping effect. Photo‐assisted carrier transport and recombination are expected to accelerate the LTD process. However, the effects of photon illumination on LTD are not investigated. Here, the effects of electrical stimulation and photo‐stimulation on the long‐term plasticity (LTP) and LTD process of photonic synaptic devices based on MoS2/h‐BN field‐effect transistors (FETs) are systemically investigated. The influences of gate dielectric layer on the photo‐induced doping are explored. The non‐volatile and electrically‐erasable properties of photo‐induced doping in MoS2/h‐BN FETs are due to the van der Waals energy barrier at the MoS2/h‐BN interface. The synaptic functions of LTP and LTD can be mimicked by the photo‐induced doping effect. The LTD process will be accelerated with the applications of positive gate voltage and laser illumination, which improves the speed of information processing. These results presented in this paper are useful for realizing high‐performance synaptic devices based on the photo‐induced doping effect.

A cracking approach to inventing new tough materials: fracture stranger than friction.

A cracking approach to inventing new tough materials: fracture stranger than friction.

Design, Synthesis, Antibacterial Evaluation and Molecular Docking Studies of Some Newer Baenzothiazole Containing Aryl and Alkaryl Hydrazides.

The alarming rise of bacterial resistance is occurring worldwide and endangering the efficacy of antibiotics. Therefore, development of new and efficient antibacterial agents remains paramount. In the present work, we designed and synthesized a series of N'-(1,3-benzothiazol-2-yl)-substituted aryl/aralkyl hydrazides C1-C27 and evaluated them in vitro for their antibacterial activity. Among all tested compounds, C10, C15, and C24 showed potent activity against Staphylococcus aureus ATCC 43300 (MRSA). Minimum bactericidal concentration studies of synthesized compounds are performed against selected bacterial strains. Time kill kinetics showed that the compounds C10 and C15 possess bactericidal activity against MRSA ATCC 43300, while compound C24 possess bactericidal activity against S. aureus NCIM 5022. In the extra-precision docking, compounds C1-C27 exhibited interactions mainly with the N-terminal and central domains of S. aureus GyrB catalytic pocket. Binding free energy (ΔGbind ) of compounds C1-C27/3U2K complexes were computed by MM-GBSA approach. Free energy components indicated Coulomb energy term as favorable for binding, while van der Waals and electrostatic solvation energy terms strongly disfavored the binding. ADMET properties of synthesized compounds C1-C27 are also computed.

Kajian Simulasi Dinamika Molekul Adsorpsi Hidrogen pada Carbone Nanotube dengan Variasi Chirality dan Temperatur Menggunakan Kode LAMMPS

Hydrogen adsorption has been simulated on carbon nanotubes for optimum hydrogen absorption. Parameters that affect the amount of hydrogen absorbed have been studied, such as the effect of chirality and temperature on hydrogen absorption in CNTs. The simulation method of hydrogen adsorption on carbone nanotubes uses molecular dynamics simulation code LAMMPS, applies Lennard-Jones interatomic potential and hydrogen atom movement using Van Der Waals force with Microcanonical Ensemble. Data analysis is the output of LAMPS in the form of data in XYZ format. The data contains information in the form of integration steps, number of atoms, temperature, pressure, potential energy, kinetic energy, volume, van der Waals energy, total simulation time and hydrogen absorption. The simulation results show that the optimum absorption occurs at run 10000 and a temperature of 100 K, for armchair chirality of 10 atoms, chirality of 12 atoms and zigzag chrality of 5 atoms. Formation of hydrogen coordinates with Avogadro software, formation of CNT coordinates with VMD software and visualization of hydrogen adsorption on CNTs using VMD software.

Vitamin D is a New Promising Inhibitor to the Main Protease (Mpro) of COVID-19 by Molecular Docking

In this study, vitamin D has shown greater efficacy of binding with Mpro of COVID-19 compared to the recently recommended drugs. The docking study was simulated to streamline interaction effects of Vitamin D, Remdesivir, Chloroquine, Hydroxychloroquine, Aspirin, and Azithromycin complexes with the active site of Mpro. Vitamin D is found to have the highest potential interaction in terms of total H-bond, van der Waal, torsional, and desolvation energy which were the lowest among all the selected drugs. The hydroxyl group of vitamin D and the thiol group of Mpro cysteine had played a leading role in increasing Vitamin D binding and stability with the Mpro pocket by contribution to the inception of three hydrogen bonds. The study recommend that vitamin D can be added to the COVID-19 treatment protocol, which may have the desired effect on viral replication inhibition and decreases mortality.

Free energy simulations to understand the effect of Met → Ala mutations at positions 205, 206 and 213 on stability of human prion protein

Prion diseases are a family of infectious amyloid diseases affecting human and animals. Prion propagation in transmissible spongiform encephalopathies is associated with the unfolding and conversion of normal cellular prion protein into its pathogenic scrapie form. Understanding the fundamentals of prion protein aggregation caused by mutations is crucial to unravel the pathology of prion diseases. To help understand the contributions of individual residues to the stability of the human prion protein, we have carried out free energy simulations based on atomistic molecular dynamics trajectories. We focus on Met → Ala mutations at positions 205, 206 and 213, which are mostly buried residues located on helix 3 of the protein. The simulations predicted that all three mutations destabilize the prion protein. Changes in unfolding free energy upon mutation, ∆∆G, are 3.10 ± 0.79, 2.00 ± 0.26 and 3.06 ± 0.66 kcal/mol for M205A, M206A and M213A, respectively, in excellent agreement with the corresponding experimental values of 3.09 ± 0.28, 1.50 ± 0.34 and 3.12 ± 0.27 kcal/mol [T. Hart et al. (2009) PNAS 106, 5651–5656]. Component analysis indicates that the major contributions to the loss of protein stability arise from van der Waals interactions for the M205A and M206A mutations, and from van der Waals and covalent energy terms for M213A. Interestingly, while free energy contributions from a majority of residues neighboring the mutation sites tend to stabilize the wild type, there are a few residues stabilizing the mutant side chains. Our results show that this approach to free energy calculation can be very useful for understanding the detailed mechanism of human prion protein stability.

Theoretical insights into molecular mechanism and energy criteria of PARP-2 enzyme inhibition by benzimidazole analogues.

The emergence of poly (ADP-ribose) polymerase (PARP) inhibitors targeting a class of PARP enzymes has gained a great interest in cancer therapy. Majority of the PARP inhibitors are not isoform-selective which may cause unwanted off-target effects. In the present study, we explore the molecular mechanism and energy requirements for PARP-2 inhibition. This involves docking studies, frontier molecular orbital analysis, 500 ns molecular dynamics simulation (MD), binding free energy analysis and principal component analysis. The results clearly suggest the importance of hydrogen bonding (Gly429, Gln332, Ser470, Tyr455) and π-π stacking interactions (His428, Tyr455, Tyr462, Phe463, Tyr473) between residues and the inhibitor. Presence of lowest unoccupied molecular orbitals favors π-π stacking interactions and highest occupied molecular orbital orbital favors hydrogen-bonding interactions in the ligands. The stability of most active/PARP-2 complex is confirmed by hydrogen bonding and π-π stacking interaction parameters. Molecular-mechanics Poisson-Boltzmann surface area energy calculations showed that van der Waals and nonpolar solvation energy terms are crucial components for the stable binding of the ligands. Per residue analysis showed that tyrosine, histidine, and phenyl alanine residues are responsible for hydrophobic interactions with the ligands. Four new inhibitors are designed based on this study and the stability of PARP-2/inhibitor complex is validated by MD, density functional theory studies, and ADME/toxicity properties. Information from the present study can serve as a basis for designing new isoform-selective PARP-2 inhibitors.

Method to determine van der Waals potential energy of particle interactions for soil clay by dynamic light scattering

AbstractSoil particle interaction forces/energies control aggregation and breakup/dispersion processes, which further profoundly affect a series of soil micro‐ and macro‐processes. For soils with complex compositions, it is the interaction energy of different particles that determines particle aggregation and aggregate breakdown/dispersion. However, measuring the interaction energy for complex systems remains a challenge. In this study we proposed a method to measure this van der Waals potential energy using the dynamic light scattering technique. Firstly, the mathematic relationship between the mean aggregation rate and van der Waals potential energy was established. The mean aggregation rates of particles for either simple or complex systems can be facilely determined by the dynamic light scattering technique. Secondly, for verifying the availability of the suggested method, montmorillonite suspensions in four different electrolyte solutions (NaCl, KCl, MgCl2 and CaCl2) were respectively employed to measure the van der Waals potential energy, which equals −17,817 ± 857 J mol−1 or −7.22 ± 0.304 kT with an average deviation of 4.22%; this directly verified the reliability of the suggested method. Thirdly, the proposed method was also verified indirectly and independently by the ratio of the electrostatic potential energy of particles to the presence of K+ and Na+, as compared with the ratios from the determined van der Waals potential energy of this study and from cation adsorption selectivity. Considering the dynamic light scattering technique has been widely applied for characterizing soil/clay/humus/microbe aggregation, the proposed method should be appropriate for measuring the van der Waals potential energy for all those systems.Highlights Develop a simple method to measure the mean interaction energy for complex systems. The mathematic relationship between the mean aggregation rate and van der Waals energy was established. A method to measure the van der Waals potential energy using the dynamic light scattering technique has been proposed. The van der Waals potential energy in the soil system can be measured in different electrolyte solutions and KCl might be the best one.

The effect of MWCNTs with different diameters on the interface properties of Ti/CFRP fiber metal laminates

Fiber-metal laminates (FMLs) consist of alternating thin layers of metal and fiber-polymer composite and are characterized by a relatively weak interface. In this paper, to address the needed improvement in the strength of the metal-resin interface, we apply molecular dynamics (MD) simulations in the design of an interface model of titanium-polyimide (Ti/PI) in which multi-walled carbon nanotubes (MWCNTs) of diameters ranging from 2 nm to 20 nm are added to PI resin to enhance the interface mechanical properties of the obtained Ti/carbon fiber-reinforced polyimide (Ti/CFRP) FMLs. As a result, these mechanical properties can be significantly improved by adding MWCNTs of different diameters to a polymer matrix. The van der Waals energy and the total energy of the system linearly increased with increasing diameter of the MWCNTs. Furthermore, the interfacial interaction energy decreased with increasing MWCNT diameter to a minimum, then increased and finally stabilized, which implied that the improvement of the interface properties followed the same trend. Notably, at an average MWCNT diameter of 8 nm, the interface fracture energy as an indication of interface mechanical performance is increased by nearly 180% compared to the material without MWCNTs.

Thermodynamic and structural aspects of molecular recognition in mannose-binding protein complexes: a theoretical study over HRP-ArtinM association.

The biomolecular recognition of D-mannose-binding lectin from Artocarpus heterophyllus (ArtinM) by Horseradish Peroxidase (HRP) mediated by glycosylation allows their application in a multitude of biological systems. The present work describes the use of molecular dynamics (MD) to assess the Gibbs free energy associated with the formation of a ArtinM-HRP conjugate mediated by a glycosylation molecule. For the enthalpy term, we applied the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method and for the vibrational entropy term, we use the quasi-harmonic approximation. Our results show that, even without glycosylation, the binding free energy between ArtinM and HRP is - 196.154 kJmol- 1, an extremely high affinity with low selectivity, originated mainly through the van der Waals energy terms. The binding free energy between ArtinM and the glycosylated HRP (gHRP) was calculated at - 66.156 kJmol- 1, an absolute and considerably lower value, however, originated from electrostatic energy terms, which increases the selectivity of molecular recognition. Our work has shown that the HRP active site region has a high affinity and low selectivity for other biomolecules. The presence of glycosylation plays a role in increasing this selectivity for this region. Thus, we conclude that performing mutagenesis of amino acid residues near the entrance of the catalytic site, can improve the activity of non-glycosylated HRPs. This illustrates new insights that can be applied to carbohydrate-based immunochemistry.

Molecular dynamics simulation of the bitumen-aggregate system and the effect of simulation details

The bitumen-aggregate interface is regarded as a significant weak link in asphalt mixtures. Therefore, the fundamental understanding of adhesion between bitumen and aggregate is crucial for designing and preserving asphalt pavement. By far, the molecular dynamics simulation method has notably attracted interest in the characterization of the bitumen-aggregate system. However, the effort towards a reasonable simulation is still ongoing. This study investigated nine cases of bitumen-aggregate systems using molecular dynamic simulations. Specifically, three bitumen binders and three mineral types were considered, respectively. In addition, mineral surface properties and some simulation details were discussed, aiming to obtain a reasonable simulation. The results indicated that polar molecules in bitumen played a vital role in the adhesion between bitumen and aggregates. The mineral surface properties in terms of mineral cleavage surface, surface atomic charge, and surface hydroxylation significantly influenced the simulation results. Accordingly, some simulation tricks were recommended for molecular dynamic simulation of bitumen-aggregate systems: (1) Geometry optimization for the mineral model is not necessary; (2) A vacuum slab with 0 Å should be added on the cleaved surface; (3) Chemical bonds should be deleted after the construction of the bitumen-aggregate system; (4) The Ewald and Atom-based methods are recommended for the energy summation of electrostatic energy and Van der Waals energy, respectively.