No description available.

Cellulose nanocrystal (CNC) has found application in a variety of novel products due to its spectrum of properties. Notably, the CNC-polymer systems have seen numerous applications in special materials like Pickering emulsions, foams and gels etc. CNC interacts with different polymers to a different extent. These interactions include molecular level and bulk interactions. Subsequently, they modify the interfacial properties. Though vibrant, the CNC-polymer molecular interaction is still unclear. We took this void in our understanding as our motivation to explore these interactions. In this work, we tried to understand why CNC interacts differently with different polymers and what drives the adsorption of polymer on CNC. Our work can also help us to understand the configurations and origins of CNC-polymer system properties. The broad range of length and time scales covered by this physical process requires a multiscale simulation approach. In this thesis, we start with the all-atom molecular simulation and focus on the specific energetic interactions between CNC surfaces and unrealistically short polymer chains. In future work, we will build on this model and develop a multiscale modeling approach for capturing the full scope of CNC-polymer interaction, including the configuration and dynamics of realistic long polymer chains around CNCs. We propose that there are two driving forces for adsorption based on the free energy difference values obtained via PMF (potential of mean force) calculations done on eight systems with different physical components. Overall, we conclude that the balance between polymer's ability to form hydrogen bonds with the surface and their interactions with the bulk solvent control the adsorption and desorption phenomenon. A larger coarse-grained model developed from our simulations will help to understand these systems better. This presented work deals with the specific energy interactions and information which we will need for the systematic coarse-graining of these systems. / Thesis / Master of Applied Science (MASc)

No description available.

Membrane proteins perform a variety of functions essential for the viability of the cell, including transport and signalling across the membrane. Most membrane proteins are formed from bundles of transmembrane helices. In this thesis molecular dynamics simulations have been used to investigate helix insertion into bilayers and helix association within bilayers. The potentials of mean force for the insertion of helices derived from the cystic fibrosis transmembrane conductance regulator into lipid bilayers were calculated using coarse-grained molecular dynamics simulations. The results showed that the insertion free energy increased with helix length and bilayer hydrophobic width. The insertion free energies obtained were significantly larger than comparable quantities obtained from translocon- mediated insertion experiments, consistent with a variety of previous studies. The implications of this observation for the interpretation of in vivo translocon-mediated insertion experiments, and the function of the translocon, are discussed. Coarse-grained and atomistic molecular dynamics simulations of the transmembrane region of the receptor tyrosine kinase EphA1 suggested that the transmembrane helix dimer was most stable when interacting via the glycine zipper motif, in agreement with a structure obtained by NMR spectroscopy. Coarse-grained simulations of the transmembrane region of EphA2 suggested that the dimer has two stable orientations, interacting via a glycine zipper or a heptad motif. Both structures showed right-handed dimers, although an NMR structure of the transmembrane region of EphA2 shows a left-handed dimer interacting via the heptad motif. Both structures obtained from coarse-grained simulations proved unstable when simulated at an atomistic level of detail. The potentials of mean force for dissociating the EphA1 and EphA2 dimers were calcu- lated using coarse-grained molecular dynamics calculations. Convergence of the detailed structure of the profiles was not conclusively shown, although association free energies cal- culated from the profiles were consistent over a variety of simulation times. The association free energies were slightly larger than experimental values obtained for comparable sys- tems, but consistent with similar computational calculations previously reported. However, direct comparisons are difficult owing to the influence of environmental factors on reported association free energies. The potential of mean force profiles showed that the interaction via the glycine zipper motif for EphA1 was significantly more stable than any other confor- mation. For EphA2 the potential of mean force profiles suggested that interaction via the glycine zipper and heptad motifs both provided stable or metastable conformations, with the interaction via the glycine zipper motif probably at least as stable as that via the heptad motif.

Molecular dynamics simulations were used to study the permeation of four different solutesthrough different cholesterol containing lipid bilayers. In all bilayers the limiting permeationbarrier shifted towards the hydrophobic core, as the cholesterol concentration was increased.Cholesterols reducing effect on the permeation rate was observed, but under certainconditions results indicating an increased permeation rate with increasing cholesterolconcentration were also obtained.

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(エネルギー科学) / 甲第19092号 / エネ博第316号 / 新制||エネ||64 / 32043 / 京都大学大学院エネルギー科学研究科エネルギー基礎科学専攻 / (主査)教授 木下 正弘, 教授 森井 孝, 教授 片平 正人 / 学位規則第4条第1項該当

京都大学 / 0048 / 新制・課程博士 / 博士(エネルギー科学) / 甲第19092号 / エネ博第316号 / 新制||エネ||64(附属図書館) / 32043 / 京都大学大学院エネルギー科学研究科エネルギー基礎科学専攻 / (主査)教授 木下 正弘, 教授 森井 孝, 教授 片平 正人 / 学位規則第4条第1項該当 / Doctor of Energy Science / Kyoto University / DFAM

Life is soft. From the fluid-like structure of lipid bilayers to the flexible folding of proteins, the realm of nanoscale soft matter is a complex and vibrant area of research. The lure of personalized medicine, advanced sensing technology, and understanding life at a fundamental level pushes research forward. This work considers to areas: (1) lipid bilayer dynamics in the presence of substrate defects and (2) the inverse temperature transition of elastic proteins. Molecular dynamics simulations as well as umbrella sampling were employed. The behavior of the bilayers discussed in the work provides evidence that small defects on confining surfaces can promote nucleation of lipid tethers. Results the second part of this work indicate elastin-like peptides experiencing inverse temperature transitions may be capable of performing amounts of work similar to RNA polymerase; additionally, resilin's inverse temperature transition may be closely linked to the molecule's ability to efficiently transmit energy through the similar coil-β secondary structure transition seen in both cases. These insights into the inverse transition temperature are relevant for the design of bio-inspired sensors and energy storage devices. / Master of Science

Le monde biologique est rempli de mystères. La compréhension de nombreux processus biologiques extrêmement complexes est grandement améliorée par la combinaison d’approches empruntées à différentes disciplines telles que la chimie et plus récemment la physique. La physique utilise des outils expérimentaux tels que les pinces optiques et les microscopies optique et électronique pour explorer les mécanismes à l’échelle microscopique se déroulant dans la cellule. La connaissance de la nature des interactions entre biomolécules et la possibilité de traduire ces interactions en équations ont permis à la physique de construire des modèles simples mais contenant les ingrédients suffisants à la description d’un mécanisme spécifique. La simulation numérique de tels modèles permet d’améliorer notre compréhension de la relation entre les mécanismes pertinents à l’échelle moléculaire et les observations expérimentales de phénomènes biologiques. / The biological world is full of mysteries. The understanding of many extremely complex biological processes is greatly improved by the combination of approaches borrowed from different disciplines such as chemistry and more recently physics. Physics uses experimental tools such as optical tweezers and optical and electron microscopes to explore the microscopic mechanisms taking place in the cell. Knowledge of the nature of the interactions between biomolecules and the possibility of translating these interactions into equations allowed physics to construct models that are simple, but contain the ingredients sufficient to describe a specific mechanism. The numerical simulation of such models improves our understanding of the relationship between relevant molecular-scale mechanisms and experimental observations of biological phenomena. The structural organization of biomolecular complexes is a process that involves various scales of length and time.

Nonequilibrium work methods for determining potentials of mean force (PMF) w(z) have recently gained popularity as an alternative to standard equilibrium based methods. Introduced by Kosztin et al., the forward-reverse (FR) method is a bidirectional work method in that it requires the work to be sampled in both forward and reverse directions along the reaction coordinate z. This bidirectional sampling leads to much faster convergence than other nonequilibrium methods such as the Jarzynski equality, and the calculation itself is extremely simple, making the FR method an attractive way of determining the PMF. Presented here is an extension to the FR method that deals with sampling problems along essentially irreversible reaction coordinates. By oscillating a particle as it is steered along a reaction coordinate, both forward and reverse work samples are obtained as the particle progresses. Dubbed the oscillating forward-reverse (OFR) method, this new method overcomes the issue of irreversibility that is present in numerous soft-matter and biological systems, particularly in the stretching or unfolding of proteins. The data analysis of the OFR method is non-trivial however, and to this end a software package named the ‘OFR Analysis Tool’ has been created. This software performs all of the complicated analysis necessary, as well as a complete error analysis that considers correlations in the data, thus streamlining the use of the OFR method for potential end users. Another attractive feature of the FR method is that the dissipative work is collected at the same time as the free energy changes, making it possible to also calculate local diffusion coefficients, D(z), from the same simulation as the PMF through the Stokes-Nernst-Einstein relation Fdrag = −γv, with γ = kB T /D. While working with the OFR method, however, the D(z) results never matched known values or those obtained through other methods, including the mean square displacement (or Einstein) method. After a reformulation of the procedure to obtain D(z), i.e. by including the correct path length and particle speeds, results were obtained that were much closer to the correct values. The results however showed very little variation over the length of the reaction coordinate, even when D(z) was known to vary drastically. It seemed that the highly variable and noncontinuous velocity function of the particle being steered through the “stiff-spring” method was incompatible with the macroscopic definition of the drag coefficient, γ. The drag coefficient requires at most a slowly varying velocity so that the assumption of a linearly related dissipative work remains valid at all times. To address this, a new dynamic constraint steering protocol (DCP) was developed to replace the previously used “stiff-spring” method, now referred to as a dynamic restraint protocol (DRP). We present here the results for diffusion in bulk water, and both the PMF and diffusion results from the permeation of a water molecule through a DPPC membrane. We also consider the issue of ergodicity and sampling, and propose that to obtain an accurate w(z) (and D(z)) from even a moderately complex system, the final result should be a weighted average obtained from numerous pulls. An additional utility of the FR and OFR methods is that the permeability across lipid bilayers can be calculated from w(z) and D(z) using the inhomogeneous solubility-diffusion (ISD) model. As tests, the permeability was first calculated for H2O and O2 through DPPC. From the simulations, the permeability coefficients for H2O were found to be 0.129 ± 0.075 cm/s and 0.141 ± 0.043 cm/s, at 323 K and 350 K respectively, while the permeability coefficients for O2 were 114 ± 40 cm/s and 101 ± 27 cm/s, again at 323 K and 350 K respectively. As a final, more challenging system, the permeability of tyramine – a positively charged trace amine at physiological pH – was calculated. The final value of P = 0.89 ± 0.24 Ang/ns is over two orders of magnitude lower than that obtained from experiment (22 ± 4 Ang/ns), although it is clear that the permeability as calculated through the ISD is extremely sensitive to the PMF, as scaling the PMF by ∼ 20% allowed the simulation and experimental values to agree within uncertainty. With accurate predictions for free energies and permeabilities, the OFR method could potentially be used for many valuable endeavors such as rational drug design.