Molecular Dynamics of Bioinspired Nanotubes

No matter how complex a model or a theory is, in the end, it is a simpler representation of reality based on our interpretations of how reality works. Consequently, the models we use might not always be either correct or accurate. However, time has shown that employing models and computations together with experimental data can provide useful information on fundamental mechanisms of the systems under study and validate or disprove proposed theories, when experiments or logic alone fail. The aim of this thesis was to study different nanomaterials and chemical compounds and obtain high resolution computational results on their structural and thermodynamic properties

Comparing Dimerization Free Energies and Binding Modes of Small Aromatic Molecules with Different Force Fields

Dimerization free energies are fundamental quantities that describe the strength of interaction of different molecules. Obtaining accurate experimental values for small molecules and disentangling the conformations that contribute most to the binding can be extremely difficult, due to the size of the systems and the small energy differences. In many cases, one has to resort to computational methods to calculate such properties. In this work, we used molecular dynamics simulations in conjunction with metadynamics to calculate the free energy of dimerization of small aromatic rings, and compared three models from popular online servers for atomistic force fields, namely G54a7, CHARMM36 and OPLS. We show that, regardless of the force field, the profiles for the dimerization free energy of these compounds are very similar. However, significant care needs to be taken when studying larger molecules, since the deviations from the trends increase with the size of the molecules, resulting in force field dependent preferred stacking modes; for example, in the cases of pyrene and tetracene. Our results provide a useful background study for using topology builders to model systems which rely on stacking of aromatic moieties, and are relevant in areas ranging from drug design to supramolecular assembly

Structural characterization of supramolecular hollow nanotubes with atomistic simulations and SAXS

Self-assembled nanostructures arise when building blocks spontaneously organize into ordered aggregates that exhibit different properties compared to the disorganized monomers. Here, we study an amphiphilic cyanine dye (C8S3) that is known to self-assemble into double-walled, hollow, nanotubes with interesting optical properties. The molecular packing of the dyes inside the nanotubes, however, remains elusive. To reveal the structural features of the C8S3 nanotubes, we performed atomistic Molecular Dynamics simulations of preformed bilayers and nanotubes. We find that different packing arrangements lead to stable structures, in which the tails of the C8S3 molecules are interdigitated. Our results are verified by SAXS experiments. Together our data provide a detailed structural characterization of the C8S3 nanotubes. Furthermore, our approach was able to resolve the ambiguity inherent from cryo-TEM measurements in calculating the wall thickness of similar systems. The insights obtained are expected to be generally useful for understanding and designing other supramolecular assemblies

Modelling structural properties of cyanine dye nanotubes at coarse-grained level

Self-assembly is a ubiquitous process spanning from biomolecular aggregates to nanomaterials. Even though the resulting aggregates can be studied through experimental techniques, the dynamic pathways of the process and the molecular details of the final structures are not necessarily easy to resolve. Consequently, rational design of self-assembling aggregates and their properties remains extremely challenging. At the same time, modelling the self-assembly with computational methods is not trivial, because its spatio-temporal scales are usually beyond the limits of all-atom based simulations. The use of coarse-grained (CG) models can alleviate this limitation, but usually suffers from the lack of optimised parameters for the molecular constituents. In this work, we describe the procedure of parametrizing a CG Martini model for a cyanine dye (C8S3) that self-assembles into hollow double-walled nanotubes. First, we optimised the model based on quantum mechanics calculations and all-atom reference simulations, in combination with available experimental data. Then, we conducted random self-assembly simulations, and the performance of our model was tested on preformed assemblies. Our simulations provide information on the time-dependent local arrangement of this cyanine dye, when aggregates are being formed. Furthermore, we provide guidelines for designing and optimising parameters for similar self-assembling nanomaterials

Using small-angle scattering and contrast matching to understand molecular packing in low molecular weight gels

It is difficult to determine exactly the molecular packing in the aggregates in low molecular weight gels. Attempts to understand the packing have been made using X-ray diffraction, but there are complications with drying and questions as to whether the crystal structures represent the packing in the gel phase. Here, we exploit contrast matching in small-angle neutron scattering experiments. By preparing selectively deuterated analogs of the same molecule, the scattering from that section of the molecule decreases compared with the hydrogenated molecule. We examine packing in the pre-gelled solutions at high pH and in the gels at low pH. The data from the final gels show a lack of specific order in the aggregates that form the gel matrix. The packing in these systems is not well ordered in the gel state and so implies that it is likely that current models and cartoons are not correct

Martini 3 Coarse-Grained Force Field:Small Molecules

The recent re-parametrization of the Martini coarse-grained force field, Martini 3, improved the accuracy of the model in predicting molecular packing and interactions in molecular dynamics simulations. Here, we describe how small molecules can be accurately parametrized within the Martini 3 framework and present a database of validated small molecule models. We pay particular attention to the description of aliphatic and aromatic ring-like structures, which are ubiquitous in small molecules such as solvents and drugs or in building blocks constituting macromolecules such as proteins and synthetic polymers. In Martini 3, ring-like structures are described by models that use higher resolution coarse-grained particles (small and tiny particles). As such, the present database constitutes one of the cornerstones of the calibration of the new Martini 3 small and tiny particle sizes. The models show excellent partitioning behavior and solvent properties. Miscibility trends between different bulk phases are also captured, completing the set of thermodynamic properties considered during the parametrization. We also show how the new bead sizes allow for a good representation of molecular volume, which translates into better structural properties such as stacking distances. We further present design strategies to build Martini 3 models for small molecules of increased complexity

Cryogenic TEM imaging of artificial light harvesting complexes outside equilibrium

The energy transport in natural light-harvesting complexes can be explored in laboratory conditions via self-assembled supramolecular structures. One such structure arises from the amphiphilic dye C8S3 molecules, which self-assemble in an aqueous medium to a double-wall cylindrical nanotube reminiscent of natural light-harvesting complexes found in green sulphur bacteria. In this paper, we report a way to investigate the structure of inner nanotubes (NTs) alone by dissolving the outer NTs in a microfluidic setting. The resulting thermodynamically unstable system was rapidly frozen, preventing the reassembly of the outer NT from the dissolved molecules, and imaged using cryogenic transmission electron microscopy (cryo-TEM). The experimental cryo-TEM images and the molecular structure were compared by simulating high-resolution TEM images, which were based on the molecular modelling of C8S3 NTs. We found that the inner NT with outer walls removed during the flash-dilution process had a similar size to the parent double-walled NTs. Moreover, no structural inhomogeneity was observed in the inner NT after flash-dilution. This opens up exciting possibilities for functionalisation of inner NTs before the reassembly of the outer NT occurs, which can be broadly extended to modify the intra-architecture of other self-assembled nanostructures

Watching Molecular Nanotubes Self-Assemble in Real Time

Molecular self-assembly is a fundamental process in nature that can be used to develop novel functional materials for medical and engineering applications. However, their complex mechanisms make the short-lived stages of self-assembly processes extremely hard to reveal. In this article, we track the self-assembly process of a benchmark system, double-walled molecular nanotubes, whose structure is similar to that found in biological and synthetic systems. We selectively dissolved the outer wall of the double-walled system and used the inner wall as a template for the self-reassembly of the outer wall. The reassembly kinetics were followed in real time using a combination of microfluidics, spectroscopy, cryogenic transmission electron microscopy, molecular dynamics simulations, and exciton modeling. We found that the outer wall self-assembles through a transient disordered patchwork structure: first, several patches of different orientations are formed, and only on a longer time scale will the patches interact with each other and assume their final preferred global orientation. The understanding of patch formation and patch reorientation marks a crucial step toward steering self-assembly processes and subsequent material engineering.</p

Molecular versus excitonic disorder in individual artificial light-harvesting systems

Natural light-harvesting antennae employ a dense array of chromophores to optimize energy transport via the formation of delocalized excited states (excitons), which are critically sensitive to spatio-energetic variations of the molecular structure. Identifying the origin and impact of such variations is highly desirable for understanding and predicting functional properties yet hard to achieve due to averaging of many overlapping responses from individual systems. Here, we overcome this problem by measuring the heterogeneity of synthetic analogues of natural antennae-self-assembled molecular nanotubes-by two complementary approaches: single-nanotube photoluminescence spectroscopy and ultrafast 2D correlation. We demonstrate remarkable homogeneity of the nanotube ensemble and reveal that ultrafast (∼50 fs) modulation of the exciton frequencies governs spectral broadening. Using multiscale exciton modeling, we show that the dominance of homogeneous broadening at the exciton level results from exchange narrowing of strong static disorder found for individual molecules within the nanotube. The detailed characterization of static and dynamic disorder at the exciton as well as the molecular level presented here opens new avenues in analyzing and predicting dynamic exciton properties, such as excitation energy transport

Multiscale modeling of molecular structure and optical properties of complex supramolecular aggregates

Supramolecular aggregates of synthetic dye molecules offer great perspectives to prepare biomimetic functional materials for light-harvesting and energy transport. The design is complicated by the fact that structure-property relationships are hard to establish, because the molecular packing results from a delicate balance of interactions and the excitonic properties that dictate the optics and excited state dynamics, in turn sensitively depend on this packing. Here we show how an iterative multiscale approach combining molecular dynamics and quantum mechanical exciton modeling can be used to obtain accurate insight into the packing of thousands of cyanine dye molecules in a complex double-walled tubular aggregate in close interaction with its solvent environment. Our approach allows us to answer open questions not only on the structure of these prototypical aggregates, but also about their molecular-scale structural and energetic heterogeneity, as well as on the microscopic origin of their photophysical properties. This opens the route to accurate predictions of energy transport and other functional properties