MD Simulation Techniques Research Articles

Design of Novel Imidazopyrazine Derivative against Breast Cancer via Targeted NPY1R Antagonist.

Breast cancer is the most frequent malignancy in women with more than one in ten new cancer diagnoses each year. Synthetic products are a key source for the identification of new anticancer medicines and drug leads. Imidazopyrazine is a highly favored skeleton for the design of new anticancer drugs. In silico designed derivatives were screened using computer aided drug design techniques and validated using MTT assay. A template-based methodology was used in the current work to create novel Imidazopyrazine derivatives, targeting the NPY1R protein. Molecular docking, Diffusion docking, MD simulation, MM-GBSA and meta-dynamics techniques were followed. MTT assay was performed to validate the activity of principal compound. A docking score of -6.660 and MMGBSA value of -108.008 (+/-) 9.14 kcal/mol was obtained from the investigations conducted. In addition, molecular dynamics simulation was carried out for 500 ns, yielding a stable RMSD and value of 5.6 Å, thus providing insights on the stability of the protein conformation on interaction with the principal compound. Furthermore, the in vivo validation studies conducted via MTT assay showed an IC50 value of 73.45 (+/-) 0.45 μg /mL. The research has produced encouraging findings and can be applied as a model for precise enumerations in the future. It also encourages the study of novel synthetic compounds with potential anti-cancer properties.

Molecular modeling study of pyrrolidine derivatives as novel myeloid cell leukemia-1 inhibitors through combined 3D-QSAR, molecular docking, ADME/Tox and MD simulation techniques

A series of pyrrolidine derivatives have been used to study the main structural requirements for designing novel Mcl-1 inhibitors. For this purpose, three models CoMSIA, CoMFA and HQSAR were generated using QSAR molecular modeling techniques. The statistical results of the CoMFA (Q2 = 0.689; R = 0.999; R2pred = 0.986), CoMSIA (Q2 = 0.614; R2 = 0.923; R2pred = 0.815) and HQSAR (Q2= 0.603; R2 = 0.662; R2pred = 0.743) models showed good stability and predictability. The results of the models were presented as contours and colored fragments indicating the favorable and unfavorable contribution to the inhibitory activity of Mcl-1. Based on the obtained results, four new compounds were designed with more potent predicted pIC50 inhibitory activity. The ADME/Tox results and the pharmacokinetic properties revealed that these four compounds are orally bioavailable and show good permeability. In addition the four compounds showing non-inhibitors of CYP3A4 and CYP2D6 with the exception of Pred03. At the level of toxicity profile, the compounds Pred01, Pred02 and Pred03 showed interesting results and showed no AMES toxicity, no hERG inhibition and no skin sensitization. Molecular docking results were used to uncover the mode of interaction between the ligand and key residues of protein binding site. Molecular docking results were supported by molecular simulation and binding free energy estimation (MMPBSA). These results demonstrate the stability of the analyzed compounds in the target protein binding site during a 100 ns trajectory. Finally, all these results create a strong lead to develop promising new Pyrrolidine-based inhibitors against Mcl-1.Communicated by Ramaswamy H. Sarma

An atomistic based continuum level 3D mode-I meso-fracture criterion for cement-based concrete

This paper establishes an atomistic based continuum level 3D mode-I meso-fracture criterion for cement-based concrete from a multiscale perspective. Firstly, on the basis of the 3D self-consistent finite stress model and the 3D mesoscale crack path model, a meso-fracture criterion is theoretically deduced by considering both the crack tip stress state and the crack path energy consumption conditions. Secondly, with the help of MD simulation technique, a systematic atomistic level modelling approach for the study of interaction behaviors between mortar and aggregate in cement-based concrete is developed, and based on which, a new determination method for the critical mesoscopic fracture index is proposed. Thirdly, using mesoscale fracture test results as experimental benchmark for numerical models, the proposed meso-fracture criterion is verified through FE simulations based on a tri-phase numerical model. It is expected this work could lay a foundation for the following investigations on concrete performance design.

Structure-Based Virtual Screening to Identify Negative Allosteric Modulators of NMDA.

NMDA (N-methyl-D-aspartate) receptor is one of the ionotropic receptor subtypes of glutamate, the most abundant excitatory neurotransmitter in the human brain. Besides physiological roles in learning and memory, neuronal plasticity and somatosensory function NMDAR overstimulation are also implicated in a pathophysiological mechanism of 'excitotoxicity.' In this study, an allosteric site has been focused on to design inhibitors of the most abundant form of this receptor of utility in many acute (stroke, traumatic brain injury) and chronic neurodegenerative diseases such as Parkinson's disease, Huntington's, Alzheimer's, and others. In order to target this specific site at the interdimer interface of the ligand-binding domain of GluN2A-containing NMDA-Rs, blood-brain barrier-permeable potentially therapeutic compounds, as opposed to only pharmacological tools currently available, were sought. Pharmacophorebased virtual screening, docking, computational ADME prediction techniques, and MD simulation studies were used. Proceeding through the in-silico methodology, the study was successful at reaching 5 compounds from ChEMBL Database, which were predicted to be potential NMDA inhibitor drugs. The products of the study are compounds that have been validated through pharmacophore and score-based screening and MD simulation techniques to be allosterically inhibiting NMDA receptors and with favorable pharmacokinetic profiles. They are likely to be therapeutic agents ready for in-vitro and in-vivo testing.

Thermomechanical properties and frictional contact behavior of oxygen doped DLC film through molecular dynamics simulation

Using the MD simulation techniques, we investigated the effects of doped oxygen atoms on the thermomechanical properties and tribological performance of diamond like carbon (DLC). The atomic percentage of oxygen (at.% O) in DLC was varied from 0 to 20.0%. The mechanical stiffness of oxidized DLC samples was evaluated using the nanoindentation simulation, while the coefficient of friction (COF) and the frictional temperature rise were obtained from the sliding contact simulation. From the simulation results, it could be found that the mechanical stiffness and the COF decreased with the at.% O in DLC. The lower COF for the oxidized DLC could be explained by the less covalent interactions with the diamond tip surface. Due to the lower stiffness, the oxidized DLC showed larger surface displacement and wear during the sliding contact. Also, the frictional temperature rise was evaluated with respect to the at.% O in DLC. The higher at.% O in DLC, the lower surface temperature rise. This could be attributed to the lower frictional heat flux and the higher specific heat of the oxidized DLC samples.

Mechanistic insight of DACH1 receptor in the development of carcinoma insurgence through MD simulation studies

Proteins are key player in the prognosis and therapeutics of carcinomas through the interactions of downstream signalling cascades. Current work insight the structural and mutational analysis of DACH1 in association with carcinogenesis. The homology modelling was employed to predict mutant and wild protein models and their reliability and accuracy was verified through multiple online approaches. Furthermore, MD simulation technique was employed to check the mutation effects on the stability of DACH1 through root mean square deviation and fluctuation graphs. Our results proposed that DACH1 mutation (C188Y) may cause lethal effects and can disturb the DACH1 structure. The observed mutational results showed that C188Y may cause some lethal effect in human body. Based on aforementioned computational assessments, it has concluded that DACH1 could be used as good therapeutic target in the prognosis and therapeutic of carcinoma insurgence. Communicated by Ramaswamy H. Sarma

Identification of Differentially Expressed Hematopoiesis-associated Genes in Term Low Birth Weight Newborns by Systems Genomics Approach.

Background Low Birth Weight (LBW) (birth weight <2.5 Kg) newborns are associated with a high risk of infection, morbidity and mortality during their perinatal period. Compromised innate immune responses and inefficient hematopoietic differentiation in term LBW newborns led us to evaluate the gene expression status of hematopoiesis.Materials and Methods In this study, we compared our microarray datasets of LBW-Normal Birth Weight (NBW) newborns with two reference datasets to identify hematopoietic stem cells genes, and their differential expression in the LBW newborns, by hierarchical clustering algorithm using gplots and RcolorBrewer package in R.Results Comparative analysis revealed 108 differentially expressed hematopoiesis genes (DEHGs), of which 79 genes were up-regulated, and 29 genes were down-regulated in LBW newborns compared to their NBW counterparts. Moreover, protein-protein interactions, functional annotation and pathway analysis demonstrated that the up-regulated genes were mainly involved in cell proliferation and differentiation, MAPK signaling and Rho GTPases signaling, and the down-regulated genes were engaged in cell proliferation and regulation, immune system regulation, hematopoietic cell lineage and JAK-STAT pathway. The binding of down-regulated genes (LYZ and GBP1) with growth factor GM-CSF using docking and MD simulation techniques, indicated that GM-CSF has the potential to alleviate the repressed hematopoiesis in the term LBW newborns.Conclusion Our study revealed that DEHGs belonged to erythroid and myeloid-specific lineages and may serve as potential targets for improving hematopoiesis in term LBW newborns to help build up their weak immune defense against life-threatening infections.

An investigation into non-covalent functionalization of a single-walled carbon nanotube and a graphene sheet with protein G:A combined experimental and molecular dynamics study

Investigation of non-covalent interaction of hydrophobic surfaces with the protein G (PrG) is necessary due to their frequent utilization in immunosensors and ELISA. It has been confirmed that surfaces, including carbonous-nanostructures (CNS) could orient proteins for a better activation. Herein, PrG interaction with single-walled carbon nanotube (SWCNT) and graphene (Gra) nanostructures was studied by employing experimental and MD simulation techniques. It is confirmed that the PrG could adequately interact with both SWCNT and Gra and therefore fine dispersion for them was achieved in the media. Results indicated that even though SWCNT was loaded with more content of PrG in comparison with the Gra, the adsorption of the PrG on Gra did not induce significant changes in the IgG tendency. Several orientations of the PrG were adopted in the presence of SWCNT or Gra; however, SWCNT could block the PrG-FcR. Moreover, it was confirmed that SWCNT reduced the α-helical structure content in the PrG. Reduction of α-helical structure of the PrG and improper orientation of the PrG-SWCNT could remarkably decrease the PrG tendency to the Fc of the IgG. Importantly, the Gra could appropriately orient the PrG by both exposing the PrG-FcR and also by blocking the fragment of the PrG that had tendency to interact with Fab in IgG.

Modelling studies determing the mode of action of anthelmintics inhibiting in vitro trehalose-6-phosphate phosphatase (TPP) of Anisakis simplex s.l

The trehalose-6-phosphate phosphatase (TPP) enzyme is involved in the synthesis of trehalose, the main sugar in the energy metabolism of nematodes. TPP is a member of the HAD-like hydrolase superfamily and shows a robust and specific phosphatase activity for the substrate trehalose-6-phosphate. The presence of conserved active sites of TPP in closely related nematodes and its absence in humans makes it a promising target for antiparasitic drugs. In the present study, homology modeling, molecular docking and MD simulation techniques were used to explore the structure and dynamics of TPP. In the active site, a magnesium ion is stabilized by 3 coordinate bonds formed by D189, D191 and D400. The key amino acids involved in ligand binding by the enzyme are C198, Y201,T357, D191 and Y197. This study relied on docking to select potential inhibitors of TPP which were tested in vitro for sensitivity to anthelmintic drugs such as levamisole and ivermectin targeting Anisakis simplex. The higher toxicity of LEV than IVM was demonstrated after 96 h, 30% of larvae were motile in cultures with 100 μg/ml of LEV and 1000 μg/ml of IVM. We identified drug combination of LEV-IVM against in vitro A. simplex as agonistic effect (CI = 1.1). Levamisole appeared to be a more effective drug which inhibited enzyme activity after 48 h and expression of mRNA after 96 h at a concentration of 10 μg/ml. This preliminary study predicted the structure of TPP, and the results of an in vitro experiment involving A. simplex will contribute to the development of effective inhibitors with potential antiparasitic activity in the future.

Mapping the intrinsically disordered properties of the flexible loop domain of Bcl-2: a molecular dynamics simulation study.

Most of the B-cell lymphoma-2 (Bcl-2) protein structure has been elucidated; however, the conformation of its flexible loop domain (FLD) has not yet been experimentally predicted. Its high flexibility under physiological conditions is the reason. FLD behaves as an intrinsically disordered region (IDR) and can adopt regular structures in particular conditions associated with the control of Bcl-2's anti-apoptotic functions. In a previous contribution, we analyzed an engineered Bcl-2 construct (Bcl-2-Δ22Σ3) submitted to 25-ns MD and reported a disordered-to-helix transitions in a region of FLD (rFLD, residues 60-77). However, the conformational preferences in solution of rFLD in the nanosecond to microsecond scale were not analyzed. Herein, an average model was obtained for the native Bcl-2 protein by homology modeling and MD simulation techniques. From this, only the atomic coordinates corresponding to the rFLD were simulated for 1 μs by MD at 310 K. In concordance with previous studies, a disordered-to-helix transitions were exhibited, implying that this "interconversion of folding" in the rFLD suggest a possible set of conformations encoded in its sequence. Principal component analysis (PCA) showed that most of the conformational fluctuation of Bcl-2 is provided by rFLD. Dihedral PCA (dPCA) offered information about all the conformations of rFLD in the μs of the simulation, characterizing a dPCA-based free energy landscape of rFLD, and a conformational ensemble of fast interconverting conformations as other IDRs. Furthermore, despite the conformational heterogeneity of rFLD, the analysis of the dihedral angles (Φ, Ψ) showed that this region does not randomly explore the conformational space in solution.

Protein conformational dynamics of crambin in crystal, solution and in the trajectories of molecular dynamics simulations

Atomic displacement parameters--B factors of the eight crambin crystal structures obtained at 0.54-1.5 angstroms resolution and temperatures of 100-293K have been analyzed. The comparable contributions to the B factor values are the intramolecular motions which are modeled by the harmonic vibration calculations and derived from the molecular dynamics simulation (MD) as well as rigid body changes in the position of a protein molecule as a whole. In solution for the average NMR structure of crambin the amplitudes of the backbone atomic fluctuations of the most residues of the segments with the regular backbone conformations are close to the amplitudes of the small scale harmonic vibrations. For the same residues the probability of the medium scale fluctuations fixed by the hydrogen exchange method is very low. The restricted conformational mobility of those segments is coupled with the depressed amplitudes of the fluctuation changes of the tertiary structure registered by the residue accessibility changes in an ensemble of NMR structures that forms the average NMR structure of crambin. The amplitudes of temperature fluctuations of backbone atoms and the tertiary structure raise in the segment with the irregular conformations, turn and loops. In the same segments the amplitudes of the calculated harmonic vibrations also increase, but to a lesser extent and especially in the interhelical loop with the most strong and complicated fluctuation changes of the backbone conformation. In solution for the NMR structure in this loop the conformational transitions occur between the conformational substates separated by the energy barriers, but they are not observed even in the long 100 ns trajectories from the MD simulation of crambin. These strong local fluctuation changes of the structure may play a key role in the protein functioning and modern performance improvements in the MD simulation techniques are oriented to increase the probability of protein appearance in the trajectories from the MD simulations.

Influence of the Water Content on the Diffusion Coefficients of Li+ and Water across Naphthalenic Based Copolyimide Cation-Exchange Membranes

The transport of lithium ions in cation-exchange membranes based on sulfonated copolyimide membranes is reported. Diffusion coefficients of lithium are estimated as a function of the water content in membranes by using pulsed field gradient (PFG) NMR and electrical conductivity techniques. It is found that the lithium transport slightly decreases with the diminution of water for membranes with water content lying in the range 14 < λ < 26.5, where λ is the number of molecules of water per fixed sulfonate group. For λ < 14, the value of the diffusion coefficient of lithium experiences a sharp decay with the reduction of water in the membranes. The dependence of the diffusion of lithium on the humidity of the membranes calculated from conductivity data using Nernst-Planck type equations follows a trend similar to that observed by NMR. The possible explanation of the fact that the Haven ratio is higher than the unit is discussed. The diffusion of water estimated by (1)H PFG-NMR in membranes neutralized with lithium decreases as λ decreases, but the drop is sharper in the region where the decrease of the diffusion of protons of water also undergoes considerable reduction. The diffusion of lithium ions computed by full molecular dynamics is similar to that estimated by NMR. However, for membranes with medium and low concentration of water, steady state conditions are not reached in the computations and the diffusion coefficients obtained by MD simulation techniques are overestimated. The curves depicting the variation of the diffusion coefficient of water estimated by NMR and full dynamics follow parallel trends, though the values of the diffusion coefficient in the latter case are somewhat higher. The WAXS diffractograms of fully hydrated membranes exhibit the ionomer peak at q = 2.8 nm(-1), the peak being shifted to higher q as the water content of the membranes decreases. The diffractograms present additional peaks at higher q, common to wet and dry membranes, but the peaks are better resolved in the wet membranes. The ionomer peak is not detected in the diffractograms of dry membranes.

Molecular dynamics simulations of plastic material deformation in machining with a round cutting edge

This paper reviews the application of the molecular dynamics simulation approach to the high-resolution visualization of the plastic material flow at the tool/workpiece interface during orthogonal cutting. MD simulation techniques have been applied to nano-scale processes, but due to restrictions in the model size and computational time, they have not been utilized to investigate processes occurring at the micro-scale. Techniques employed to extend the MD simulation techniques to the micro-scale are discussed. Preferred ranges for model parameters that provide for sufficient resolution in order to adequately describe the characteristic features of the plastic material flow, yet achieve significant reduction in the model computational times, are identified. An investigation of the plastic material flow at the tool/workpiece interface as the uncut chip thickness increases from 10% to 90% of the edge radius of the tool was undertaken. A key observation is that there is a marked variation in the geometry of the observed characteristic features, most notable being the rotation and growth of the stable built-up edge as the uncut chip thickness increases. Furthermore, the transition between the plowing and cutting regimes is observed.

Computer Simulations of Alzheimer's Beta Amyloid Interactions with Multicomponent Lipid Bilayers

Amyloidogenic protein unfolding and subsequent aggregation on cell surfaces are linked to many protein misfolding diseases, e.g., Alzheimer's (AD) and Parkinson's. Beta-amyloid (betaA), a 39 to 43 residue peptide, is released from neuronal membranes upon sequential proteolytic cleavages of a large transmembrane amyloid precursor protein by two secretases. An understanding of the conformational transitions and stability mediated by the lipid surface interactions is important for developing new strategies for the prevention and treatment of protein misfolding diseases. Using all-atom MD simulation techniques, we explore the initial folding and lipid insertion kinetics of betaA of both 40 and 42 residue long on the surfaces of well-defined lipid nanodomains with different cholesterol contents that mimic the neuronal lipid membranes. Several molecular clusters consisting of different initial conformations, alpha-barrel, beta-sheet and globular-coil, of betaA and stable mixed lipid bilayer in explicit solvent have successfully been constructed. The conformational transitions and stability of betaA on the lipid surface and in a partially inserted state on lipid nanodomains of different lipid compositions were systematically studied. The protein-induced membrane disruptions were examined by calculating the lipid order parameter, water permeability and bilayer thickness profiles of the lipid bilayers. The time-dependent secondary structure of betaA was used to gauge the unfolding events of the protein and its dependence on the lipid composition of the interacting bilayers. Our results revealed that the cholesterol content in the lipid bilayer strongly affects the initial lipid surface-induced unfolding and bilayer-insertion and stability behavior of betaA in our model bilayer systems. Our computer simulation data may provide useful computational insights on the controversial sensitization and protective roles of lipid membranes on the protein aggregation events in AD.

In Silico Study of Full-Length Amyloid β 1−42 Tri- and Penta-Oligomers in Solution

Amyloid oligomers are considered to play causal roles in the pathogenesis of amyloid-related degenerative diseases including Alzheimer's disease. Using MD simulation techniques, we explored the contributions of the different structural elements of trimeric and pentameric full-length Abeta1-42 aggregates in solution to their stability and conformational dynamics. We found that our models are stable at a temperature of 310 K, and converge toward an interdigitated side-chain packing for intermolecular contacts within the two beta-sheet regions of the aggregates: beta1 (residues 18-26) and beta2 (residues 31-42). MD simulations reveal that the beta-strand twist is a characteristic element of Abeta-aggregates, permitting a compact, interdigitated packing of side chains from neighboring beta-sheets. The beta2 portion formed a tightly organized beta-helix, whereas the beta1 portion did not show such a firm structural organization, although it maintained its beta-sheet conformation. Our simulations indicate that the hydrophobic core comprising the beta2 portion of the aggregate is a crucial stabilizing element in the Abeta aggregation process. On the basis of these structure-stability findings, the beta2 portion emerges as an optimal target for further antiamyloid drug design.

Geometric confinement governs the rupture strength of H-bond assemblies at a critical length scale

ABSTRACTUsing theoretical considerations and MD simulation techniques, we show that the rupture strength of H-bond assemblies is governed by geometric confinement effects, suggesting that clusters of at most 3-4 H-bonds break concurrently, even under uniform shear loading of a much larger number of H-bonds. This universally valid result leads to an intrinsic strength limitation that suggests that shorter strands with less H-bonds achieve the highest shear strength. Our finding explains how the intrinsic strength limitation of H-bonds is overcome by the formation of a nanocomposite structure of H-bond clusters, thereby enabling the formation larger, much stronger beta-sheet structures. Our results explain recent experimental proteomics data, suggesting a correlation between the shear strength and the prevalence of beta-strand lengths in biology.

A Novel Integrated X‐Ray Powder Diffraction (XRPD) and Molecular Dynamics (MD) Approach for Modelling Mixed‐Metal (Zn, Al) Layered Double Hydroxides (LDHs).

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Molecular dynamics simulation study of the effect of PMMA tacticity on free volume morphology in membranes

The effect of the tacticity of poly methyl methacrylate (PMMA) on the morphology of free volume in PMMA membranes was studied by using a molecular dynamics simulation technique. The chain flexibility, chain interaction, end-to-end distance of a chain and the time course of the free volume variation in the various stereo-regular PMMA, were obtained by an MD simulation technique. Simulation results depict that the construction of distinct tacticity has a significant influence on the flexibility of a molecular chain and the morphology of free volume in the syndiotactic (s-) and isotactic (i-) PMMA oligomers. MD calculation of the dynamic microstructure of a PMMA matrix shows that the s-PMMA membrane gives less flexibility in the backbone and a longer end-to-end distance than in the i-PMMA membrane. The less flexibility and longer end-to-end distance in the s-PMMA matrix causes the shapes and sizes of s-PMMA free volume to be longer and larger than those in an i-PMMA membrane. Furthermore, by adopting conformation energy minimization and molecular dynamics simulation techniques, various tacticity models of PMMA were constructed and their effect on the size of accessible free volume and free volume morphology was analyzed. Finally, the adsorbed gas on the surface free volume in s-PMMA was also compared with i-PMMA membrane.

A molecular dynamics study of the structural stability of HIV‐1 protease under physiological conditions: The role of Na+ ions in stabilizing the active site

HIV-1 protease is most active under weakly acidic conditions (pH 3.5-6.5), when the catalytic Asp25 and Asp25' residues share 1 proton. At neutral pH, this proton is lost and the stability of the structure is reduced. Here we present an investigation of the effect of pH on the dynamics of HIV-1 protease using MD simulation techniques. MD simulations of the solvated HIV-1 protease with the Asp25/25' residues monoprotonated and deprotonated have been performed. In addition we investigated the effect of the inclusion of Na(+) and Cl(-) ions to mimic physiological salt conditions. The simulations of the monoprotonated form and deprotonated form including Na(+) show very similar behavior. In both cases the protein remained stable in the compact, "self-blocked" conformation in which the active site is blocked by the tips of the flaps. In the deprotonated system a Na(+) ion binds tightly to the catalytic dyad shielding the repulsion between the COO(-) groups. Ab initio calculations also suggest the geometry of the active site with the Na(+) bound closely resembles that of the monoprotonated case. In the simulations of the deprotonated form (without Na(+) ions), a water molecule bound between the Asp25 Asp25' side-chains. This disrupted the dimerization interface and eventually led to a fully open conformation.

Dynamics of Ganglioside Headgroup in Lipid Environment: Molecular Dynamics Simulations of GM1 Embedded in Dodecylphosphocholine Micelle

Recognition of membrane-anchored glycosphingolipid receptors by various ligands is the key event in several biological phenomena. However, mere presence of these cell-surface receptors does not always ensure their recognition and binding by their respective ligands, a phenomenon termed “crypticity”. Earlier studies have suggested that different glycan headgroup orientations exposing and/or masking different epitopes may explain the crypticity of glycolipids. The effect of lipid environment on the orientation and conformation of GM1 ganglioside has been investigated in the present study by MD simulation technique in an attempt to understand the structural basis of crypticity. In addition, the effect of the length of the ceramide hydrocarbon tails on the headgroup conformation has also been investigated. MD simulations for 1 ns were performed with explicit water molecules for both GM1 headgroup (GM1-Os) and GM1 embedded in dodecylphosphocholine micelle. The simulations show that the conformations of the hyd...