Molecular dynamics simulation of single-walled carbon nanotubes inside liquid crystals

Molecular dynamic simulations of systems of single-walled carbon nanotubes (CNTs) in liquid crystalline solvents were performed, in order to investigate the effect of the molecular structure and phase of the liquid crystal (LC) on the interactions between the CNTs. Three different LC molecules (5CB, 8CB and 5CF) were considered in our study. Our results with 5CB and 8CB suggest that increasing the chain length of the hydrophobic part of the LC molecule by three carbon atoms is insufficient to decrease the tendency for the CNTs to aggregate in the LCs. Additionally, varying the phase of the LC is also insufficient to decrease the aggregation tendency of the CNTs. However, simulations with 5CF (which has fluorine atoms in the head group of the LC molecule) suggest that this LC solvent can decrease the tendency of the CNTs to aggregate. This study is relevant to assist experimentalists with the development of high-quality dispersions of large concentrations of CNTs in the LCs.     

A molecular mechanics and semiempirical molecular orbital study on the conformation of polynorbornene chains

The conformational analysis of polynorbornene (PNB) chains was investigated with the AM1, MM2, AMBER and OPLS methods taking into consideration the possibility of binding of norbornene monomers to each other at various positions, i.e. exo–exo, exo–endo, endo–endo. The chain that is formed by connecting exo–endo positions of the monomers has lower torsional barrier energy than those formed with bonds at other positions and has more flexibility. It is determined that the thredisyndiotactic chain formed by exo–endo addition adopts a helix structure and has a coil shape. The disyndiotactic chain formed by connecting norbornene monomers in mixed type has a linear structure. It is found that the repeat unit conformations of thredisyndiotactic and disyndiotactic chains of PNB are TGTG^– and (TGTG^–)₂, respectively.     

The molecular structure of the IsiA-Photosystem I supercomplex, modelled from high-resolution, crystal structures of Photosystem I and the CP43 protein

We present the molecular structure of the IsiA-Photosystem I (PSI) supercomplex, inferred from high-resolution, crystal structures of PSI and the CP43 protein. The structure of iron-stress-induced A protein (IsiA) is similar to that of CP43, albeit with the difference that IsiA is associated with 15 chlorophylls (Chls), one more than previously assumed. The membrane-spanning helices of IsiA contain hydrophilic residues many of which bind Chl. The optimal structure of the IsiA-PSI supercomplex was inferred by systematically rearranging the IsiA monomers and PSI trimer in relation to each other. For each of the 6,969,600 structural configurations considered, we counted the number of optimal Chl-Chl connections (i.e., cases where Chl-bound Mg atoms are ≤ 25 Å apart). Fifty of these configurations were found to have optimal energy-transfer potential. The 50 configurations could be divided into three variants; one of these, comprising 36 similar configurations, was found to be superior to the other configurations in terms of its potential to transfer excitation energy to the reaction centres under low-light conditions and its potential to dissipate excess energy under high-light conditions. Compared to the assumed model [Biochemistry 42 (2003) 3180-3188], the new Chl increases by 7% the ability of IsiA to harvest sunlight while the rearrangement of the constituent components of the IsiA-PSI supercomplex increases by 228% the energy-transfer potential. In conclusion, our model allows us to explain how the IsiA-PSI supercomplex may act as an efficient light-harvesting structure under low-light conditions and as an efficient dissipater of excess energy under high-light conditions.     

Molecular dynamics calculations on peroxidases: the effect of calcium ions on protein structure

 Molecular dynamics (MD) calculations were performed on two peroxidases, lignin peroxidase (LiP) and horseradish peroxidase (HRP), in the presence of the two endogenous calcium ions. The resulting averaged structures were compared to the structures obtained in the absence of the calcium ions. The overall protein folding was not affected by the presence or the lack of the calcium ions, while the active site was perturbed. In particular, on the distal side, a sizeable rearrangement of the distal histidine was observed in the absence of the calcium ions. These structural rearrangements are critically discussed with respect to the enzymatic mechanism. Received: 15 November 1995 / Accepted: 1 March 1996     

A note on the hypothesis: Protein polymorphism as a phase of molecular evolution

Summary Assuming that various kinds of balancing selection contribute only a small fraction of naturally occuring genetic variation, it is shown that if a fair fraction of evolutionary change in protein is due to neutral mutants, most of naturally occurring polymorphism must be due to random drift of neutral genes.     

Concentration effect of cimetidine with POPC bilayer: a molecular dynamics simulation study

All-atom molecular dynamics simulations have been performed on cimetidine in the presence of a palmitoyloleoylphosphatidylcholine (POPC) bilayer. The free energy profile of a single cimetidine molecule passing across POPC bilayer displays a minimum at the interface of bilayer and water. Ten cimetidine molecules were inserted into POPC bilayer to obtain an 8 mol % drug model, and molecular dynamics results showed that cimetidine molecules reside at the polar region of POPC bilayer with sulphur atoms directing to the hydrophobic region. By comparing the one drug model with 8 mol % drug model, one can see that the central barrier to cross the membrane increases while the free energy in bulk water decreases, indicating that the ability of cimetidine passing across the POPC bilayer weakens at increased concentration. In addition, the free energy minimum shifts closer to the hydrophobic core. Our results indicate that with the increased drug concentration, it is more difficult for cimetidine to enter and pass across POPC bilayer.     

Molecular dynamics simulation of human interleukin-4: comparison with NMR data and effect of pH,counterions and force field on tertiary structure stability

The human protein interleukin-4 (IL-4) has been simulated at two different pH values 2 and 6, with different amounts of counterions present in the aqueous solution, and with two different force-field parameter sets using molecular dynamics simulation with the aim of validation of force field and simulation set-up by comparison to experimental nuclear magnetic resonance data, such as proton–proton nuclear Overhauser effect (NOE) distance bounds, ³ J(HN,HC_α) coupling constants and backbone N–H order parameters. Thirteen simulations varying in the length from 3 to 7 ns are compared.

At pH 6 both force-field parameter sets used do largely reproduce the NOE's and order parameters, the GROMOS 45A3 set slightly better than the GROMOS 53A6 set. ³ J values predicted from the simulation agree less well with experimental values. At pH 2 the protein unfolds, unless counterions are explicitly present in the system, but even then the agreement with experiment is worse than at pH 6. When simulating a highly charged protein, such as IL-4 at pH 2, the inclusion of counterions in the simulation seems mandatory.     

Molecular aspects of the interaction between amphotericin B and a phospholipid bilayer: molecular dynamics studies

Amphotericin B (AmB) is a polyene macrolide antibiotic used to treat systemic fungal infections. The molecular mechanism of AmB action is still only partly characterized. AmB interacts with cell-membrane components and forms membrane channels that eventually lead to cell death. The interaction between AmB and the membrane surface can be regarded as the first (presumably crucial) step on the way to channel formation. In this study molecular dynamics simulations were performed for an AmB–lipid bilayer model in order to characterize the molecular aspects of AmB–membrane interactions. The system studied contained a box of 200 dimyristoylphosphatidylcholine (DMPC) molecules, a single AmB molecule placed on the surface of the lipid bilayer and 8,065 water molecules. Two molecular dynamics simulations (NVT ensemble), each lasting 1 ns, were performed for the model studied. Two different programs, CHARMM and NAMD2, were used in order to test simulation conditions. The analysis of MD trajectories brought interesting information concerning interactions between polar groups of AmB and both DMPC and water molecules. Our studies show that AmB preferentially took a vertical position, perpendicular to the membrane surface, with no propensity to enter the membrane. Our finding may suggest that a single AmB molecule entering the membrane is very unlikely.Figure The figure presents the whole structure of the system simulated—starting point. AmB is presented as a space-filling model, DMPC molecules—green sticks, water molecules—red sticks     

Selected biologically relevant ions at the air/water interface: a comparative molecular dynamics study

Interfacial behavior of selected biologically and technologically relevant ions is studied using molecular dynamics simulations employing polarizable potentials. Propensities of choline, tetraalkylammonium (TAA), and sodium cations, and sulfate and chloride anions for the air/water interface are analyzed by means of density profiles. Affinity of TAA ions for the interface increases with their increasing hydrophobicity. Tetramethylammonium favors bulk solvation, whereas cations with propyl and butyl chains behave as surfactants. The choice of counter-anions has only a weak effect on the behavior of these cations. For choline, sodium, chloride and sulfate, the behavior at the air/water interface was compared to the results of our recent study on the segregation of these ions at protein surfaces. No analogy between these two interfaces in terms of ion segregation is found.     

1H NMR study of the effect of variable ligand on heme oxygenase electronic and molecular structure

Heme oxygenase carries out stereospecific catabolism of protohemin to yield iron, CO and biliverdin. Instability of the physiological oxy complex has necessitated the use of model ligands, of which cyanide and azide are amenable to solution NMR characterization. Since cyanide and azide are contrasting models for bound oxygen, it is of interest to characterize differences in their molecular and/or electronic structures. We report on detailed 2D NMR comparison of the azide and cyanide substrate complexes of heme oxygenase from Neisseria meningitidis, which reveals significant and widespread differences in chemical shifts between the two complexes. To differentiate molecular from electronic structural changes between the two complexes, the anisotropy and orientation of the paramagnetic susceptibility tensor were determined for the azide complex for comparison with those for the cyanide complex. Comparison of the predicted and observed dipolar shifts reveals that shift differences are strongly dominated by differences in electronic structure and do not provide any evidence for detectable differences in molecular structure or hydrogen bonding except in the immediate vicinity of the distal ligand. The readily cleaved C-terminus interacts with the active site and saturation-transfer allows difficult heme assignments in the high-spin aquo complex.     

Micro-environment effect on the structure of synthetic substrates of thermolysin

Summary The conformations of thermolysin synthetic substrates in H₂O/D₂O (9/1) and glycerol-d ₅ (5 M) are investigated using two-dimensional nuclear magnetic resonance spectroscopy and molecular modeling. The structures obtained from molecular modeling and NMR studies are compared. Comparisons of these structures with bound inhibitor in the active site of thermolysin are also discussed.     

Micro-environment effect on the structure of synthetic substrates of thermolysin

The conformations of thermolysin synthetic substrates inH₂O/D₂O (9/1) and glycerol-d₅ (5 M) are investigated using two-dimensional nuclearmagnetic resonance spectroscopy and molecular modeling. The structuresobtained from molecular modeling and NMR studies are compared. Comparisonsof these structures with bound inhibitor in the active site of thermolysinare also discussed.     

Molecular imprinting of nitrophenol and hydroxybenzoic acid isomers: effect of molecular structure and acidity on imprinting

Three nitrophenol isomer-imprinted polymers were prepared under the same conditions using 4-vinylpyridine as a functional monomer. Different recognition capacities for template molecules were observed for the three polymers. Another imprinting system with stronger acidity than nitrophenol isomers, 2-hydroxybenzoic acid (salicylic acid) and 4-hydroxybenzoic acid, was imprinted using 4-vinylpyridine or acrylamide as functional monomer respectively. Both 4-hydroxybenzoic acid-imprinted polymers using the two monomers showed recognition ability for the template molecule. However, when acrylamide was chosen as functional monomer, the salicylic acid-imprinted polymer showed very weak recognition for the template molecule, whereas strong recognition ability of the resultant polymer for salicylic acid was observed with 4-vinylpyridine as functional monomer. It seems that the structure and acidity of template molecules is responsible for the difference in recognition, by influencing the formation and strength of interaction between template molecule and functional monomer during the imprinting process. An understanding of the mechanism of molecular imprinting and molecular recognition of MIPs will help to predict the selectivity of MIPs on the basis of template molecule properties.     

Molecular mechanism of Ferula asafoetida for the treatment of asthma: Network pharmacology and molecular docking approach

Asthma is a significant health-care burden that has great impact on the quality of life of patients and their families. The limited amount of previously reported data and complicated pathophysiology of asthma make it a difficult to treat and significant economic burden on public healthcare systems. Ferula asafoetida is an herbaceous, monoecious, perennial plant of the Umbelliferae family. In Asia, F. asafoetida is used to treat a range of diseases and disorders, including asthma. Several in vitro studies demonstrated the therapeutic efficacy of F. asafoetida against asthma. Nevertheless, the precise molecular mechanism is yet to be discovered. In the framework of current study, network pharmacology approach was used to identify the bioactive compounds of F. asafoetida in order to better understand its molecular mechanism for the treatment of asthma. In present work, we explored a compound-target-pathway network and discovered that assafoetidin, cynaroside, farnesiferol-B, farnesiferol-C, galbanic-acid, and luteolin significantly influenced the development of asthma by targeting MAPK3, AKT1 and TNF genes. Later, docking analysis revealed that active constituents of F. asafoetida bind stably with three target proteins and function as asthma repressor by regulating the expression of MAPK3, AKT1 and TNF genes. Thus, integration of network pharmacology with molecular docking revealed that F. asafoetida prevent asthma by modulating asthma-related signaling pathways. This study lays the basis for establishing the efficacy of multi-component, multi-target compound formulae, as well as investigating new therapeutic targets for asthma.     

蛋白激酶C同工酶分子结构及功能研究进展

蛋白激酶Ｃ（ＰＫＣ）是至少包括１１种亚型在内的丝／苏氨酸蛋白激酶家族,可分为传统型（ｃＰＫＣｓ）、新型（ｎＰＫＣｓ）、非典型（ａＰＫＣｓ）和ＰＫＣ－ｕ四大类。各ＰＫＣ亚型在ＡＴＰ结合位点、磷脂酰基转移位点、假性底物位点、佛波酯结合位点的氨基酸序列既高度保守又有变异。ＰＫＣ在机体内分布和作用十分广泛,本文主要介绍了ＰＫＣ在肿瘤形成、侵润和转移及肿瘤耐药性产生,调节造血干／祖细胞定向分化成熟,以及激素     

Investigation of the inhibition pathway of glucosamine synthase by N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid by semiempirical quantum mechanical and molecular mechanics methods

Glucosamine synthase (E.C. 2.6.1.16) is a promising target in antifungal drug design. It has been reported that its potent inhibitor, N³-(4-methoxyfu-maroyl)-L-2,3-diaminopropanoic acid (FMDP), inactivates the enzyme by the Michael addition of the S-H group to the FMDP molecule followed by cyclisation reactions. In this study we have investigated, by means of semiempirical MNDO, PM3 and molecular mechanics methods, the energetics and kinetic possibility of the formation of various stereoisomers of the products of cyclisation of the Michael addition products detected experimentally. It was found that the substituted 1,4-thiazin-3-one can be formed in one step under alkaline conditions; the stereoisomers of this compound predicted to be the most stable on the basis of theoretical calculations are also the dominant ones in reality.Abbreviations FMDP N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid - MNDO Modified Neglect of Diatomic Overlap - AM1 Advanced Method 1 - PM3 (full abbreviation: MNDOPM3) Modified Neglect of Diatomic Overlap, Parametrised Method 3 Correspondence to: A. Liwo     

The molecular mechanics program DUPLEX: Computing structures of carcinogen modified DNA by surveying the potential energy surface

The nucleic acids molecular mechanics program DUPLEX has been designed with useful features for surveying the potential energy surface of polynucleotides, especially ones that are modified by polycyclic aromatic carcinogens. The program features helpful strategies for addressing the multiple minimum problem: (1) the reduced variable domain of torsion angle space; (2) search strategies that emphasize large scale searches for smaller subunits, followed by building to larger units by a variety of strategies; (3) the use of penalty functions to aid the minimizer in locating selected structural types in first stage minimizations; penalty functions are released in terminal minimizations to yield final unrestrained minimum energy conformations. Predictive capability is illustrated by DNA modified by activated benzo[a]pyrenes.