Simulations Of Aqueous Solutions Research Articles

Counter-ion adsorption and electrostatic potential in sodium and choline dodecyl sulfate micelles - a molecular dynamics simulation study.

Choline-based surfactants are interesting both from the practical point of view to obtaining environmental-friendly surfactants as well as from the theoretical side since the interactions between the choline and surfactants can help to understand self-assembly phenomena in deep eutectic solvents. Although no significant change was noticed in the micelle size and shape due to the exchange of the sodium counter-ion by choline in our simulations, the adsorption of the choline cation over the micelle surface is stronger than the adsorption of the sodium, which leads to a reduction of the exposed surface area of the micelle and remarkable effects over the electrostatic potential. The choline neutralizes the surface charge of the surfactant better than sodium; however, this is partially compensated by a stronger water orientation around the SDS micelle. The balance between the contributions from the surfactant, the counter-ion, and water to the electrostatic potential leads to a complex pattern with alternate regions of positive and negative potential at the micelle/water interface which can be important to the incorporation of other charged species at the micelle surface as well as for the interaction between micelles in solution. To evaluate the effects of the counter-ion substitution, micelles of sodium dodecyl sulfate (SDS) and choline dodecyl sulfate (ChDS) were studied and compared by means of molecular dynamics simulations in aqueous solution. In both cases, the simulations started from pre-assembled micelles with 60 dodecyl sulfate ions and 240-ns simulations were performed at NPT ensemble at T = 323.15K and P = 1bar using the Gromacs software with the OPLS-AA force field to describe dodecyl sulfate and choline, Åqvist parameters for sodium, and SPC model for water molecules.

Investigating the potential of natural compounds as novel inhibitors of SARS-CoV-2 RdRP using computational approaches

ABSTRACT COVID-19 is a highly contagious disease caused by SARS-CoV-2. Currently, no vaccines or antiviral treatments are available to combat this deadly virus; however, precautions and some repurposed medicines are available to contain COVID-19. RNA-dependent RNA polymerase (RdRP) plays an important role in the replication or transcription of viral mechanisms. Approved antiviral drug such as Remdesivir has shown inhibitory activity against SARS-CoV-2 RdRP. The purpose of this study was to carry out a rational screening of natural products against SARS-CoV-2 RdRP, which may serve as a basis to develop a treatment option against COVID-19. For this purpose, a protein and structure conservation analysis of SARS-CoV-2 RdRP was performed to check mutations. A library of 15,000 phytochemicals was developed from literature review, ZINC database, PubChem and MPD3 database; and was used to performed molecular docking and molecular dynamics simulation (MD) analysis. The top-ranked compounds were subjected to pharmacokinetic and pharmacological studies. Among them, top 7 compounds (Spinasaponin A, Monotropane, Neohesperidoe, Posin, Docetaxel, Psychosaponin B2, Daphnodrine M, and Target Remedesvir) were noticed to interact with the active site residues. MD simulation in aqueous solution suggested conformational flexibility of loop regions in the complex to stabilize the docked inhibitors. Our study revealed that the studied compounds have potential to bind to the active site residues of SARS-CoV-2 RdRP. Although, this computational work is not experimentally determined but the structural information and selected compounds might help in the design of antiviral drugs targeting SAR-CoV-2 by inhibiting the activity of SARS-CoV-2 RdRP.

Computational investigation of conformational fluctuations of Aβ42 monomers in aqueous ionic liquid mixtures

Aggregation of intrinsically disordered proteins (IDPs) is often triggered by protein–protein interaction, leading to several neurodegenerative diseases.In this study, we aim to understand the role of 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM][BF4] ionic liquid (IL) on altering secondary structure of the peptide and study the interactions responsible for their conformational modification. Here we report structural features of an ensemble of amyloid beta (Aβ42) peptide monomers employing all-atom molecular dynamics simulations in aqueous solution of IL at room temperature. Our calculations reveal, Aβ42 peptide exhibit rapidly inter-converting conformations adopting extended chain as well as collapsed coil-like structures with a propensity to form few transient α-helices and β-sheets at intermediate times. We have correlated this higher flexibility of the peptide with formation of less stable salt-bridge in presence of IL in aqueous solution. It is found that water molecules around the polar regions are more structured imparting structural rigidity to the peptide backbone than around the hydrophobic domains. Thus identifying the effect of electrostatic interaction of IL on expulsion of water molecules from the polar domains on the peptide surface can shed light on preventing the aggregation process. We have also determined the most energetically stable peptide conformations from various accessible intermediate states using metadynamics simulations that are characterized by the rugged free energy surface having multiple energy basins.

Molecular screening of glycyrrhizin-based inhibitors against ACE2 host receptor of SARS-CoV-2.

The interaction between SARS-CoV-2 Spike protein and angiotensin-converting enzyme 2 (ACE2) is essential to viral attachment and the subsequent fusion process. Interfering with this event represents an attractive avenue for the development of therapeutics and vaccine development. Here, a hybrid approach of ligand- and structure-based virtual screening techniques were employed to disclose similar analogues of a reported antiviral phytochemical, glycyrrhizin, targeting the blockade of ACE2 interaction with the SARS-CoV-2 Spike. A ligand-based similarity search using a stringent cut-off revealed 40 FDA-approved compounds in DrugBank. These filtered hits were screened against ACE2 using a blind docking approach to determine the natural binding tendency of the compounds with ACE2. Three compounds, deslanoside, digitoxin, and digoxin, were reported to show strong binding with ACE2. These compounds bind at the H1-H2 binding pocket, in a manner similar to that of glycyrrhizin which was used as a control. To achieve consistency in the docking results, docking calculations were performed via two sets of docking software that predicted binding energy as ACE2-Deslanoside (AutoDock, −10.3 kcal/mol and DockThor, −9.53 kcal/mol), ACE2-Digitoxin (AutoDock, −10.6 kcal/mol and DockThor, −8.84 kcal/mol), and ACE2-Digoxin (AutoDock, −10.6 kcal/mol and DockThor, −8.81 kcal/mol). The docking results were validated by running molecular simulations in aqueous solution that demonstrated the stability of ACE2 with no major conformational changes in the ligand original binding mode (~ 2 Å average RMSD). Binding interactions remained quite stable with an increased potential for getting stronger as the simulation proceeded. MMGB/PBSA binding free energies were also estimated and these supported the high stability of the complexes compared to the control (~ −50 kcal/mol net MMGB/PBSA binding energy versus ~ −30 kcal/mol). Collectively, the data demonstrated that the compounds shortlisted in this study might be subjected to experimental evaluation to uncover their real blockade capacity of SARS-CoV-2 host ACE2 receptor.Graphical abstract

Nature of the bond, reduction potential, and solvation properties of ruthenium nitrosyl complexes of the type trans‐[Ru(NH3)4(L)(NO)]2+/3+ and [Ru(salen)(L)(NO)]2+/3+ in different charge and spin states

AbstractIn this work, we present a systematic study of the nature of the RuNO bond, reduction potential, and behavior in the solution of several ruthenium nitrosyl complexes of the type trans‐[Ru(NH3)4(L)(NO)]2+/3+ (L = Cl, H2O, NH3, OH, py = pyridine, POEt3 = triethylphosphite, TVP = trivinyl phosphite) and [Ru(salen)(L)(NO)]2+/3+ (L = Cl, H2O) in different charge and spin states. We employed density functional theory, complete active space self‐consistent field, the quantum theory of atoms in molecules, charge decomposition analysis, and Monte Carlo statistical simulation in aqueous solution to investigate how the different ligands on the coordination sphere of the ruthenium atom can affect the nature of the RuNO bond and, therefore, its reactivity, reduction potential, and solvation properties. The nature of the RuNO bond varies significantly between the singlet, doublet, and triplet electronic states of these complexes, in part due to the change in the coordination mode of the NO ligand and also due to the electron correlation effects along the RuNO bond that changes drastically. For all complexes studied, the RuNO bond shows some intriguing characteristics, such as large kinetic energy density and considerable amount of electron localization between the atoms, besides high multiconfigurational character, with a significant contribution from the RuIIINO0 configuration. In addition, for all the complexes investigated, the NO ligand does not interact with the solvent through hydrogen bonds, making this group accessible for chemical reactions in solution. Another important finding was that some of the RuIIINO compounds can be reduced by biological reducing agents in the singlet ground state, while all of them have high reduction potentials in the triplet excited state, making them suitable candidates for the photorelease of nitric oxide.

Stilbene-based natural compounds as promising drug candidates against COVID-19

The pandemic coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a great threat to public health. Currently, no potent medicine is available to treat COVID-19. Quest for new drugs especially from natural plant sources is an area of immense potential. The current study aimed to repurpose stilbenoid analogs, reported for some other biological activities, against SARS-CoV-2 spike protein and human ACE2 receptor complex for their affinity and stability using molecular dynamics simulation and binding free energy analysis based on molecular docking. Four compounds in total were probed for their binding affinity using molecular docking. All of the compounds showed good affinity (> −7 kcal/mol). However, fifty nanoseconds molecular dynamic simulation in aqueous solution revealed highly stable bound conformation of resveratrol to the viral protein: ACE2 receptor complex. Net free energy of binding using MM-PBSA also affirmed the stability of the resveratrol-protein complex. Based on the results, we report that stilbene based compounds in general and resveratrol, in particular, can be promising anti-COVID-19 drug candidates acting through disruption of the spike protein. Our findings in this study are promising and call for further in vitro and in vivo testing of stiblenoids, especially resveratrol against the COVID-19. Communicated by Ramaswamy H. SarmaHighlightsStilbenoid analogs could be potential disruptors of SARS-CoV-2 spike protein and human ACE2 receptor complex.In particular, resveratrol revealed highly stable conformation to the viral protein: ACE2 receptor complex.The strong interaction of resveratrol is affirmed by molecular dynamic simulation studies and better net free energies.

Aggregation Patterns in Low- and High-Charge Anions Define Opposite Solubility Trends.

Molecular dynamics simulations in aqueous solution reveal the existence of two distinct patterns of aggregation in low and high charge density Lindqvist-type polyoxometalates (POMs). Our results indicate the presence of contact and solvent-shared ion pairs and specific and preferential interactions of alkalis with POMs. Highly charged POMs are capable of breaking apart the Li+ and Cs+ solvation shell, thus enhancing the formation of long-lived alkali-POM contact ion pairs, where alkalis act as an electrostatic "glue" forming large oligomers. Stronger ion pair interactions for Li+ than for Cs+ promote lower solubility for Li+ than for Cs+, evoking anomalous solubility trends. Lower charge density POMs are not capable of disrupting the Li+ solvation shell and only solvent-shared ion pairs are formed, whereas for Cs+, contact ion pairs exist. The large number of oxygen atoms in the POM surface enhances the hydrogen bonds between POM and water, thus promoting aggregation. In this case, aggregation follows normal solubility trends. Thus, aggregation depends on the strength of ion pair interactions, the capacity of POM to disrupt alkali's solvation shell, and the contact surface area between the solvent and POM.

Blocking the catalytic mechanism of MurC ligase enzyme from Acinetobacter baumannii: An in Silico guided study towards the discovery of natural antibiotics

Acinetobacter baumannii belongs to the most critical group of bacterial pathogens that are resistant to large number of antibiotics, including the highly effective carbapenems and third generation cephalosporins. Novel antibiotics targeting unique pathways of the said pathogen could reduce the mortality rate due to its infections that are impervious to the current antibiotics. Herein, we explored a library of natural compounds that was filtered first for drug-like, followed by lead-like molecules, which were finally utilized in structure based virtual screening to identify the most promising inhibitor for the Ligand binding (LB) domain of MurC ligase enzyme. The inhibitor (1′-((2H-imidazol-2-yl)methyl)-N-(pyridin-2-yl)-1′,2′-dihydro-[4,4′-bipyridin]-2-amine) was observed with a conformation to target most conserved and catalytically critical residues of both the intended LB as well as the ATP binding domain of MurC. This multi-domain inhibitor revealed to have an excellent pharmacokinetics profile thus likely to have safe and effective therapeutic applications for the future. Molecular dynamics simulation in aqueous solution further supported the high affinity of the compound for the target site involving strong hydrogen bonding. At residue level, radial distribution function (RDF) and axial distribution function (AFD) illustrated Asp334 as the most critical amino acid that drives recognition, binding, and activity of the compound. The complex stability was validated by subjecting it to Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA), Molecular Mechanics Generalized Born Surface Area (MMGBSA) and WaterSwap based binding free energy calculations. The system was observed with high stability: total binding energy in MMGBSA (−48.45 kcal/mol) and MMPBSA (−3.62 kcal/mol). The columbic interactions were noticed to dominate (−336.90 kcal/mol), followed by van der Waals energies (−45.52 kcal/mol) in MurC-inhibitor binding. The absolute binding free energy estimated by WaterSwap was −43.2 kcal/mol, depicting higher complex stability. The screened scaffold might be used in functional groups substitution to achieve further lead optimization.

Comparative prediction of binding affinity of Hydroxyurea anti-cancer to boron nitride and carbon nanotubes as smart targeted drug delivery vehicles

In this study, the adsorption of Hydroxyurea (HU) onto the inner and outer surfaces of boron nitride and carbon nanotubes (CNTs) was investigated using the density functional theory calculations and molecular dynamics (MDs) simulations in aqueous solution. The values of the adsorption energy show that HU molecule is preferentially adsorbed inside of boron nitride and CNTs with the molecular axis parallel to the tubes axis, which means that the cavity of nanotubes is favorable for encapsulation of this drug. Also, it was found that the HU/boron nitride nanotube (BNNT) system is more stable than the HU/CNT system. The stability of the complexes of HU/ BNNT attributed to the formation of the intermolecular hydrogen bonds between the H atoms of HU molecule and the N atoms of BNNT, which is confirmed by Bader’s quantum theory of atoms in molecules. The natural bond orbital analysis shows the charge transfers occur from HU molecule to nanotubes in all complexes. Moreover, the adsorption of HU molecule on the surfaces of the nanotubes was investigated by explicit water models. Also, the adsorption behavior of HU on the functionalized boron nitride and CNTs is investigated to design and develop new nanocarriers for biomedical applications. Furthermore, MDs simulations are examined in the presence of one and two drug molecules. The obtained results illustrate that the lowest value of Lennard–Jones (L–J) energy between drug and nanotubes exist in the simulation system with two drug molecules.

From phylogeny to protein dynamics: A computational hierarchical quest for potent drug identification against an emerging enteropathogen “Yersinia enterocolitica”

Yersinia enterocolitica is an enteric bacterium categorized as the third most common cause of bacterial diarrhea in Europe. The pathogen exhibits an intrinsic resistance to several antibiotics, which is exacerbated by the absence of a vaccine. This prompts a quest for novel drug targets, to tackle the alarming threat to human health caused by multiple-drug resistant Y. enterocolitica. Subtractive proteomics have revealed that Pyridoxine 5′-phosphate synthase enzyme is a safe target for novel inhibitors, as it is involved in the pathogen's essential Pyridoxine 5′-phosphate pathway. Structure based virtual screening has led to the identification of a natural drug-like compound, 2-acetyl-3-(2-heptanamidoethyl)-1H-indol-6-yl heptanoate that demonstrated a high affinity to the enzyme active site in docking studies. Furthermore, molecular dynamics (MD) simulations in aqueous solution confirm that the compound remains stable in the enzyme's active site throughout the simulation. ASN18 was identified as playing a significant role in mediating strong hydrogen bonding and hydrophobic interactions between the compound and the enzyme active site. Binding free energy calculations using the Molecular Mechanics – Generalized Born Surface Area (MMGBSA) and WaterSwap methods also predict that the compound binds to the enzyme with high affinity. The data from the present work is encouraging and will aid in the discovery of novel antibiotics against this deadly pathogen.

Temperature effect on the structure and conformational fluctuations in two zinc knuckles from the mouse mammary tumor virus

Zinc fingers are small protein domains in which zinc plays a structural role, contributing to the stability of the zinc–peptide complex. Zinc fingers are structurally diverse and are present in proteins that perform a broad range of functions in various cellular processes, such as replication and repair, transcription and translation, metabolism and signaling, cell proliferation, and apoptosis. Zinc fingers typically function as interaction modules and bind to a wide variety of compounds, such as nucleic acids, proteins, and small molecules. In this study, we investigated the structural properties, in solution, of the proximal and distal zinc knuckles of the nucleocapsid (NC) protein from the mouse mammary tumor virus (MMTV) (MMTV NC). For this purpose, we performed a series of molecular dynamics simulations in aqueous solution at 300 K, 333 K, and 348 K. The temperature effect was evaluated in terms of root mean square deviation of the backbone atoms and root mean square fluctuation of the coordinating residue atoms. The stability of the zinc coordination sphere was analyzed based upon the time profile of the interatomic distances between the zinc ions and the chelator atoms. The results indicate that the hydrophobic character of the proximal zinc finger is dominant at 333 K. The low mobility of the coordinating residues suggests that the strong electrostatic effect exerted by the zinc ion on its coordinating residues is not influenced by the increase in temperature. The evolution of the structural parameters of the coordination sphere of the distal zinc finger at 300 K gives us a reasonable picture of the unfolding pathway, as proposed by Bombarda and coworkers (Bombarda et al., 2005), which can predict the binding order of the four conserved ligand-binding residues. Our results support the conclusion that the structural features can vary significantly between the two zinc knuckles of MMTV NC.

Identification of Rare Lewis Oligosaccharide Conformers in Aqueous Solution Using Enhanced Sampling Molecular Dynamics.

Determining the conformations accessible to carbohydrate ligands in aqueous solution is important for understanding their biological action. In this work, we evaluate the conformational free-energy surfaces of Lewis oligosaccharides in explicit aqueous solvent using a multidimensional variant of the swarm-enhanced sampling molecular dynamics (msesMD) method; we compare with multi-microsecond unbiased MD simulations, umbrella sampling, and accelerated MD approaches. For the sialyl Lewis A tetrasaccharide, msesMD simulations in aqueous solution predict conformer landscapes in general agreement with the other biased methods and with triplicate unbiased 10 μs trajectories; these simulations find a predominance of closed conformer and a range of low-occupancy open forms. The msesMD simulations also suggest closed-to-open transitions in the tetrasaccharide are facilitated by changes in ring puckering of its GlcNAc residue away from the 4C1 form, in line with previous work. For sialyl Lewis X tetrasaccharide, msesMD simulations predict a minor population of an open form in solution corresponding to a rare lectin-bound pose observed crystallographically. Overall, from comparison with biased MD calculations, we find that triplicate 10 μs unbiased MD simulations may not be enough to fully sample glycan conformations in aqueous solution. However, the computational efficiency and intuitive approach of the msesMD method suggest potential for its application in glycomics as a tool for analysis of oligosaccharide conformation.

Characterization of the interaction forces in a drug carrier complex of doxorubicin with a drug-binding peptide.

Polypeptide-based materials are used as building blocks for drug delivery systems aimed at toxicity decrease in chemotherapeutics. A molecular-level approach is adopted for investigating the non-covalent interactions between doxorubicin and a recently synthesized drug-binging peptide as a key part of a system for delivery to neoplastic cells. Molecular dynamics simulations in aqueous solution at room and body temperature are applied to investigate the structure and the binding modes within the drug-peptide complex. The tryptophans are outlined as the main chemotherapeutic adsorption sites, and the importance of their placement in the peptide sequence is highlighted. The drug-peptide binging energy is evaluated by density functional theory calculations. Principal component analysis reveals comparable importance of several types of interaction for the binding strength. π-Stacking is dominant, but other factors are also significant: intercalation, peptide backbone stacking, electrostatics, dispersion, and solvation. Intra- and intermolecular H-bonding also stabilizes the complexes. The influence of solvent molecules on the binding energy is mild. The obtained data characterize the drug-to-peptide attachment as a mainly attractive collective process with interactions spanning a broad range of values. These results explain with atomistic detail the experimentally registered doxorubicin-binging ability of the peptide and outline the complex as a prospective carrying unit that can be employed in design of drug delivery systems.

Stabilities and Dynamics of Protein Folding Nuclei by Molecular Dynamics Simulation**Supported by the National Basic Research Program of China under Grant No. 2013CB932804, the National Natural Science Foundation of China under Grant No. 11421063, and the CAS Biophysics Interdisciplinary Innovation Team Project

To understand how the stabilities of key nuclei fragments affect protein folding dynamics, we simulate by molecular dynamics (MD) simulation in aqueous solution four fragments cut out of a protein G, including one α-helix (seqB: KVFKQYAN), two β-turns (seqA: LNGKTLKG and seqC: YDDATKTF), and one β-strand (seqD: DGEWTYDD). The Markov State Model clustering method combined with the coarse-grained conformation letters method are employed to analyze the data sampled from 2-μs equilibrium MD simulation trajectories. We find that seqA and seqB have more stable structures than their native structures which become metastable when cut out of the protein structure. As expected, seqD alone is flexible and does not have a stable structure. Throughout our simulations, the native structure of seqC is stable but cannot be reached if starting from a structure other than the native one, implying a funnel-shape free energy landscape of seqC in aqueous solution. All the above results suggest that different nuclei have different formation dynamics during protein folding, which may have a major contribution to the hierarchy of protein folding dynamics.

Structural and Dynamical Properties of Tetraalkylammonium Bromide Aqueous Solutions: A Molecular Dynamics Simulation Study Using a Polarizable Force Field

Understanding the behavior of aqueous solutions containing tetraalkylammonium (TAA) cations is of great significance in a number of applications, including polymer membranes for fuel cells. In this work, a polarizable force field has been used to perform atomistic molecular dynamics (MD) simulations of aqueous solutions containing tetramethylammonium (TMA) or tetrabutylammonium (TBA) cations and Br counterions. Extensive MD simulations of TMA-Br/water and TBA-Br/water systems were conducted as a function of solution composition (ion pair:water molar ratios of 1:10, 1:20, 1:30, 1:63, and 1:500) at atmospheric pressure and 298 K. Our simulations demonstrate excellent agreement with available experimental data for solution densities and diffusion coefficients of different species as a function of solution composition, providing us confidence in analyzed structural and dynamic correlations. Various ion-ion and ion-water spatial distributions and the extent of cation aggregation are discussed in light of changes in the structure of cations hydration shells. The delicate balance between cation ionic core interactions with water and the hydrophobic interactions of alkyl tails leads to nontrivial self-assembly of TAA cations and the formation of an interpenetrating cationic network at higher concentrations. The ions and water dynamics are strongly coupled with the observed structural correlations and are analyzed in terms of various residence time, diffusion coefficients, and ionic conductivity.

Small static electric field strength promotes aggregation-prone structures in amyloid-β(29-42).

The formation of senile plaques in central neural system resulting from the aggregation of the amyloid β (Aβ) of 40 and 42 residues is one of the two hallmarks of Alzheimer's disease. Numerous experiments and computational studies have shown that the aggregation of Aβ peptides in vitro is very complex and depends on many factors such as pH, agitation, temperature, and peptide concentration. The impact of a static electric field (EF) on amyloid peptide aggregation has been much less studied, although EFs may have some applications to treat Parkinson's disease symptoms. Here, we study the influence of an EF strength of 20 mV/nm, present in the human brains, on the conformation of the Aβ29-42 dimer. Our 7 μs non-equilibrium atomistic simulations in aqueous solution show that this field-strength promotes substantially the formation of β-hairpins, believed to be a very important intermediate state during aggregation. This work also suggests that structural biology experiments conducted under appropriate EF strengths may help reduce the conformational heterogeneity of Aβ1-40/Aβ1-42 dimers and provide significant insights into their structures that may be disease-causing.

Proton Exchange in a Paramagnetic Chemical Exchange Saturation Transfer Agent from Experimental Studies and ab Initio Metadynamics Simulation.

The proton-exchange process between water and a carbamate has been studied experimentally and theoretically in a lanthanide-based paramagnetic chemical exchange saturation transfer agent endowed with potential multimodality detection capabilities (optical imaging, or T1 MRI for the Gd(III) analogue). In addition to an in-depth structural analysis by a combined approach (using X-ray crystallography, NMR, and molecular dynamics), our ab initio simulation in aqueous solution sheds light on the reaction mechanism for this proton exchange, which involves structural Grotthuss diffusion.

Studying the adsorption of DNA nanostructures on graphene in the aqueous phase using molecular dynamic simulations

DNA nanostructures can undergo large structural fluctuations and deviate from their intended configurations. In this work, two model DNA nanostructures (i.e., Nan and Kai) were designed based on the shape of the two Chinese characters of the name of Nankai University, and additional single-stranded DNA fragments were added to interact with graphene. During four 50-ns molecular dynamic simulations in aqueous solution, the DNA nanostructures adsorbed onto graphene demonstrated more stable conformations with lower root mean square deviations and smaller coordinate changes in the z-axis direction than the DNA nanostructures that were not adsorbed onto graphene. The interaction analyses and energetic calculations show that π-π interactions between single-stranded DNA and graphene are necessary for adsorption of the DNA nanostructures. Overall, this work examined the interactions between DNA and graphene at a large spatial scale with the hope that it provides a new strategy to stabilize DNA nanostructures.

Coarse‐grained and All‐atom Simulations towards the Early and Late Steps of Amyloid Fibril Formation

AbstractAlzheimer's disease is the most common neurodegenerative disease. Experiments and computer simulations can complement one another to provide a full and in‐depth understanding of many aspects in the amyloid field at the atomistic level. Here, we review results of our coarse‐grained and all‐atom simulations in aqueous solution aimed at determining: 1) early aggregation steps of short linear peptides; 2) nucleation size number; 3) solution structure of the Aβ1–40/Aβ1–42 wild‐type dimers; 4) impact of FAD (familial forms of Alzheimer's disease) mutations on the structure of Aβ1–40/Aβ1–42 dimers; and 5) impact of protective mutations on the structure of Aβ1–40/Aβ1–42 dimers.

Stability of a Split Streptomycin Binding Aptamer.

Here we investigated the stability of an aptamer, which is formed by two RNA strands and binds the antibiotic streptomycin. Molecular dynamics simulations in aqueous solution confirmed the geometry and the pattern of hydrogen bond interactions that was derived from the crystal structure (1NTB). The result of umbrella sampling simulations indicated a favored streptomycin binding with a free energy of ΔGbind° = −101.7 kJ mol–1. Experimentally, the increase in oligonucleotide stability upon binding of streptomycin was probed by single-molecule force spectroscopy. Rate dependent force spectroscopy measurements revealed a decrease in the natural off-rate (koff-COMPLEX = 0.22 ± 0.16 s–1) for the aptamer–streptomycin complex compared to the aptamer having an empty binding pocket (koff-APTAMER = 0.49 ± 0.11 s–1). This decrease in the natural off-rate corresponds to a decrease in the Gibbs free energy of ΔΔGsheer ≈ −3.4 kJ mol–1. The simulated binding pattern and the experimental results led to the conclusion that...