Jukka Määttä

Toward Atomistic Resolution Structure of Phosphatidylcholine Headgroup and Glycerol Backbone at Different Ambient Conditions

Phospholipids are essential building blocks of biological membranes. Despite a vast amount of very accurate experimental data, the atomistic resolution structures sampled by the glycerol backbone and choline headgroup in phoshatidylcholine bilayers are not known. Atomistic resolution molecular dynamics simulations have the potential to resolve the structures, and to give an arrestingly intuitive interpretation of the experimental data, but only if the simulations reproduce the data within experimental accuracy. In the present work, we simulated phosphatidylcholine (PC) lipid bilayers with 13 different atomistic models, and compared simulations with NMR experiments in terms of the highly structurally sensitive C–H bond vector order parameters. Focusing on the glycerol backbone and choline headgroups, we showed that the order parameter comparison can be used to judge the atomistic resolution structural accuracy of the models. Accurate models, in turn, allow molecular dynamics simulations to be used as an interpretation tool that translates these NMR data into a dynamic three-dimensional representation of biomolecules in biologically relevant conditions. In addition to lipid bilayers in fully hydrated conditions, we reviewed previous experimental data for dehydrated bilayers and cholesterol-containing bilayers, and interpreted them with simulations. Although none of the existing models reached experimental accuracy, by critically comparing them we were able to distill relevant chemical information: (1) increase of choline order parameters indicates the P–N vector tilting more parallel to the membrane, and (2) cholesterol induces only minor changes to the PC (glycerol backbone) structure. This work has been done as a fully open collaboration, using nmrlipids.blogspot.fi as a communication platform; all the scientific contributions were made publicly on this blog. During the open research process, the repository holding our simulation trajectories and files (https://zenodo.org/collection/user-nmrlipids) has become the most extensive publicly available collection of molecular dynamics simulation trajectories of lipid bilayers.

Carbon nanotube bundling: influence on layer-by-layer assembly and antimicrobial activity

Antimicrobial surfaces are needed for many health care applications. Single walled carbon nanotubes (SWNT) have shown promise as antimicrobial agents, but important questions persist concerning the effects of tube bundling, a common phenomenon owing to strong hydrophobicity. We investigate here the influence of bundling on the layer-by-layer (LbL) assembly of SWNT with charged polymers, and on the antimicrobial properties of the resultant films. We employ a poly(ethylene glycol) functionalized phospholipid (PL-PEG) to disperse SWNT in aqueous solution, and consider cases where SWNT are dispersed (i) as essentially isolated objects and (ii) as small bundles. Quartz crystal microgravimetry with dissipation (QCMD) and ellipsometry measurements show the bundled SWNT system to adsorb in an unusually strong fashion – with layers twice (when hydrated) and three times (when dried) as thick as those of isolated SWNT. Molecular dynamics simulation reveals a lower PL-PEG density and degree of solution extension on bundled versus isolated SWNT, suggesting thicker adsorbed layers may result from suppressed steric repulsion between bundled nanotubes. Enhanced van der Waals attraction in the bundled system may also play a role. Scanning electron micrographs reveal Escherichia coli on films with bundled SWNT to be essentially engulfed by the nanotubes, whereas the bacteria rest upon films with isolated SWNT. While both systems inactivate 90% of bacteria in 24 h, the bundled SWNT system is “fast-acting,” reaching this inactivation rate in 1 h. This study demonstrates the significant impact of SWNT bundling on LbL assembly and antimicrobial activity, explores the molecular basis of nanotube–nanotube interactions, and demonstrates the possibility of bacteria-engulfing, fast-acting, SWNT-based antimicrobial coatings.

Controlling carbon-nanotube-phospholipid solubility by curvature dependent self-assembly

Control of aqueous dispersion is central in the processing and usage of nanoscale hydrophobic objects. However, selecting dispersive agents based on the size and form of the hydrophobic object and the role of coating morphology in dispersion efficiency remain important open questions. Here, the effect of the substrate and the dispersing molecule curvature, as well as, the influence of dispersant concentration on the adsorption morphology are examined by molecular simulations of graphene and carbon nanotube (CNT) substrates with phospholipids of varying curvature as the dispersing agents. Lipid spontaneous curvature is increased from close to zero (effectively cylindrical lipid) to highly positive (effectively conical lipid) by studying double tailed dipalmitoylphosphadidylcholine (DPPC) and single tailed lysophosphadidylcholine (LPC) which differ in the number of acyl chains but have identical headgroup. We find that lipids are good dispersion agents for both planar and curved nanoparticles and induce a dispersive barrier nonsize selectively. Differences in dispersion efficiency arise from lipid headgroup density and their extension from the hydrophobic substrate in the adsorption morphology. We map the packing morphology contributing factors and report that the aggregate morphologies depend on the competition of interactions rising from (1) hydrophobicity driven maximization of lipid-substrate contacts and lipid self-adhesion, (2) tail bending energy cost, (3) preferential alignment along the graphitic substrate principal axes, and (4) lipid headgroup preferential packing. Curved substrates adjust the morphology by changing the balance between the interaction strengths. Jointly, the findings show substrate curvature and dimensions are a way to tune lipid adsorption to desired, self-assembling patterns. Besides engineering dispersion efficiency, the findings could bear significance in designing materials with defined molecular scale, molecular coatings for orientation specific CNT assembly or lipid-based molecular masks and patterning on graphene.

Energy band alignment and electronic states of amorphous carbon surfaces in vacuo and in aqueous environment

In this paper, we obtain the energy band positions of amorphous carbon (a–C) surfaces in vacuum and in aqueous environment. The calculations are performed using a combination of (i) classical molecular dynamics (MD), (ii) Kohn-Sham density functional theory with the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional, and (iii) the screened-exchange hybrid functional of Heyd, Scuseria, and Ernzerhof (HSE). PBE allows an accurate generation of a-C and the evaluation of the local electrostatic potential in the a-C/water system, HSE yields an improved description of energetic positions which is critical in this case, and classical MD enables a computationally affordable description of water. Our explicit calculation shows that, both in vacuo and in aqueous environment, the a-C electronic states available in the region comprised between the H2/H2O and O2/H2O levels of water correspond to both occupied and unoccupied states within the a-C pseudogap region. These are localized states associated to sp2 ...

Intrinsic α-helical and β-sheet conformational preferences: A computational case study of alanine

A fundamental question in protein science is what is the intrinsic propensity for an amino acid to be in an α‐helix, β‐sheet, or other backbone dihedral angle ( ϕ ‐ψ) conformation. This question has been hotly debated for many years because including all protein crystal structures from the protein database, increases the probabilities for α‐helical structures, while experiments on small peptides observe that β‐sheet‐like conformations predominate. We perform molecular dynamics (MD) simulations of a hard‐sphere model for Ala dipeptide mimetics that includes steric interactions between nonbonded atoms and bond length and angle constraints with the goal of evaluating the role of steric interactions in determining protein backbone conformational preferences. We find four key results. For the hard‐sphere MD simulations, we show that (1) β‐sheet structures are roughly three and half times more probable than α‐helical structures, (2) transitions between α‐helix and β‐sheet structures only occur when the backbone bond angle τ (NCαC) is greater than 110°, and (3) the probability distribution of τ for Ala conformations in the “bridge” region of ϕ ‐ψ space is shifted to larger angles compared to other regions. In contrast, (4) the distributions obtained from Amber and CHARMM MD simulations in the bridge regions are broader and have increased τ compared to those for hard sphere simulations and from high‐resolution protein crystal structures. Our results emphasize the importance of hard‐sphere interactions and local stereochemical constraints that yield strong correlations between ϕ ‐ψ conformations and τ.

Simulations Study of Single-Component and Mixed n-Alkyl-PEG Micelles

Here, we study one-component and mixed n-alkyl-poly(ethylene glycol) (CmEn) micelles with varying poly(ethylene glycol) (PEG) chain lengths n using coarse-grained molecular simulations. These nonionic alkyl-PEG surfactants and their aggregates are widely used in bio and chemical technology. As expected, the simulations show that increasing the PEG chain length decreases the alkyl-PEG micelle core diameter and the aggregation number but also enhances PEG chain penetration to the core region and spreads the micelle corona. Both the core and corona density are heavily dependent on the PEG chain length and decrease with increasing PEG length. Furthermore, we find that the alkyl-PEG surfactants exhibit two distinct micellization modes: surfactants with short PEG chains as their hydrophilic heads aggregate with the PEG heads relatively extended. Their aggregation number and the PEG corona density are dictated by the core carbon density. For longer PEG chains, the PEG sterics, that is, the volume occupied by the PEG head group, becomes the critical factor limiting the aggregation. Finally, simulations of binary mixtures of alkyl-PEGs of two different PEG chain lengths show that even in the absence of core-freezing, the surfactants prefer the aggregate size of their single-component solutions with the segregation propelled via enthalpic contributions. The findings, especially as they provide a handle on the density and the density profile of the aggregates, raise attention to effective packing shape as a design factor of micellar systems, for example, drug transport, solubilization, or partitioning.

Intrinsic α-helical and β-sheet conformational preferences: A computational case study of alanine: Intrinsic α-Helical and β-Sheet Conformational Preferences

A fundamental question in protein science is what is the intrinsic propensity for an amino acid to be in an α‐helix, β‐sheet, or other backbone dihedral angle ( ϕ ‐ψ) conformation. This question has been hotly debated for many years because including all protein crystal structures from the protein database, increases the probabilities for α‐helical structures, while experiments on small peptides observe that β‐sheet‐like conformations predominate. We perform molecular dynamics (MD) simulations of a hard‐sphere model for Ala dipeptide mimetics that includes steric interactions between nonbonded atoms and bond length and angle constraints with the goal of evaluating the role of steric interactions in determining protein backbone conformational preferences. We find four key results. For the hard‐sphere MD simulations, we show that (1) β‐sheet structures are roughly three and half times more probable than α‐helical structures, (2) transitions between α‐helix and β‐sheet structures only occur when the backbone bond angle τ (NCαC) is greater than 110°, and (3) the probability distribution of τ for Ala conformations in the “bridge” region of ϕ ‐ψ space is shifted to larger angles compared to other regions. In contrast, (4) the distributions obtained from Amber and CHARMM MD simulations in the bridge regions are broader and have increased τ compared to those for hard sphere simulations and from high‐resolution protein crystal structures. Our results emphasize the importance of hard‐sphere interactions and local stereochemical constraints that yield strong correlations between ϕ ‐ψ conformations and τ.

Intrinsic alpha-helical and beta-sheet preferences: A computational case study of Alanine

A fundamental question in protein science is what is the intrinsic propensity for an amino acid to be in an α‐helix, β‐sheet, or other backbone dihedral angle ( ϕ ‐ψ) conformation. This question has been hotly debated for many years because including all protein crystal structures from the protein database, increases the probabilities for α‐helical structures, while experiments on small peptides observe that β‐sheet‐like conformations predominate. We perform molecular dynamics (MD) simulations of a hard‐sphere model for Ala dipeptide mimetics that includes steric interactions between nonbonded atoms and bond length and angle constraints with the goal of evaluating the role of steric interactions in determining protein backbone conformational preferences. We find four key results. For the hard‐sphere MD simulations, we show that (1) β‐sheet structures are roughly three and half times more probable than α‐helical structures, (2) transitions between α‐helix and β‐sheet structures only occur when the backbone bond angle τ (NCαC) is greater than 110°, and (3) the probability distribution of τ for Ala conformations in the “bridge” region of ϕ ‐ψ space is shifted to larger angles compared to other regions. In contrast, (4) the distributions obtained from Amber and CHARMM MD simulations in the bridge regions are broader and have increased τ compared to those for hard sphere simulations and from high‐resolution protein crystal structures. Our results emphasize the importance of hard‐sphere interactions and local stereochemical constraints that yield strong correlations between ϕ ‐ψ conformations and τ.