Maria Stepanova

A detailed process characterization of SML electron beam resist for high-aspect-ratio nanopatterning at high sensitivity is presented. SML contrast curves were generated for methyl isobutyl ketone (MIBK), MIBK/isopropyl alcohol (IPA) (1:3), IPA/water (7:3), n-amyl acetate, xylene, and xylene/methanol (3:1) developers. Using IPA/water developer, the sensitivity of SML was improved considerably and found to be comparable to benchmark polymethylmethacrylate (PMMA) resist without affecting the aspect ratio performance. Employing 30-keV exposures and ultrasonic IPA/water development, an aspect ratio of 9:1 in 50-nm half-pitch dense grating patterns was achieved representing a greater than two times improvement over PMMA. Through demonstration of 25-nm lift-off features, the pattern transfer performance of SML is also addressed.

Exposure of polymethylmethacrylate (PMMA) during electron beam lithography (EBL) produces small polymer fragments that dissolve rapidly during the development process. The resist dissolution behavior varies greatly depending on the nature of the developer (solvent) and therefore influences the selection of the EBL parameters, such as dose (sensitivity). A molecular scale examination of the development process is necessary to elucidate the resist–developer interaction mechanisms. In this work, the authors investigate the interaction of short PMMA chains (containing up to 10 MMA units) with common developer components methyl isobutyl ketone (MIBK) and isopropyl alcohol (IPA). For this purpose, the authors conduct molecular dynamics simulations using the Accelrys Materials Studio package. The simulation results were used to characterize the mixtures in the spirit of the Flory–Huggins theory of polymers and also to extract the diffusivities. The authors found that the behavior of PMMA fragments differed considerably in MIBK as compared with IPA. PMMA fragments containing more than three monomers exhibit stronger attractive interaction with MIBK. For all fragment sizes simulated, the diffusivity of PMMA fragments is 60–160% higher in MIBK as well. Similarly, the authors observed differences in the gyration radii. The authors conclude that the kinetic factor seems to be more significant as compared to affinity factor when accounting for differences in exposure sensitivities due to developer selection.

Essential collective dynamics is a promising and robust approach for analysing the slow motions of macromolecules from short molecular dynamics trajectories. In this study, an extension of the method to treat a collection of interacting protein molecules is presented. The extension is applied to investigate the effects of dimerization on the collective dynamics of ovine prion protein molecules in two different arrangements. Examination of the structural plasticity shows that aggregation has a restricting effect on the local mobility of the prion protein molecules in the interfacial regions. Domain motions of the two dimeric ovine prion protein conformations are distinctly different and can be related to interatomic correlations at the interface. Correlated motions are among the slow collective modes extensively analysed by considering both main‐chain and side‐chain atoms. Correlation maps reveal the existence of a vast network of dynamically correlated side groups, which extends beyond individual subunits via interfacial interconnections. The network is formed by a core of hydrophobic side chains surrounded by hydrophilic groups at the periphery. The relevance of these findings are discussed in the context of mutations associated with prion diseases. The binding free energy of the dimeric conformations is evaluated to probe their thermodynamic stability. The descriptions afforded by the analysis of the essential collective dynamics of the prion dimers are consistent with their binding free energies. The agreement validates the extension of the methodology and provides a means of interpreting the collective dynamics in terms of the thermodynamic stability of ovine prion proteins. Proteins 2012.

A novel theoretical methodology is described that allows the identification of dynamic structural domains and the analysis of local flexibility in proteins. The methodology employs a multiscale approach that combines definition of essential collective coordinates based on the covariance analysis of molecular dynamics trajectories, construction of the Mori projection operator with these essential coordinates and analysis of the corresponding generalised Langevin equations. The domains are associated with relatively stable regions in the protein, whereas off-domain regions are relatively soft. The applications include the domain coarse-graining and characterisation of the local flexibility in protein G and prion proteins. The results are compared with published NMR experiments. The methodology is apt to provide rigorous dynamic scores and characterisation tools for structural biology, bioinformatics and rational drug design.

Collective motions on ns-μs time scales are known to have a major impact on protein folding, stability, binding and enzymatic efficiency. It is also believed that these motions may have an important role in the early stages of prion protein misfolding and prion disease. In an effort to accurately characterize these motions and their potential influence on the misfolding and prion disease transmissibility we have conducted a combined analysis of molecular dynamic simulations and NMR-derived flexibility measurements over a diverse range of prion proteins. Using a recently developed numerical formalism, we have analyzed the essential collective dynamics (ECD) for prion proteins from 8 different species including human, cow, elk, cat, hamster, chicken, turtle and frog. We also compared the numerical results with flexibility profiles generated by the random coil index (RCI) from NMR chemical shifts. Prion protein backbone flexibility derived from experimental NMR data and from theoretical computations show strong agreement with each other, demonstrating that it is possible to predict the observed RCI profiles employing the numerical ECD formalism. Interestingly, flexibility differences in the loop between second beta strand (S2) and the second alpha helix (HB) appear to distinguish prion proteins from species that are susceptible to prion disease and those that are resistant. Our results show that the different levels of flexibility in the S2-HB loop in various species are predictable via the ECD method, indicating that ECD may be used to identify disease resistant variants of prion proteins, as well as the influence of prion proteins mutations on disease susceptibility or misfolding propensity.

Kinetic Monte Carlo Simulation of Metallic Nanoislands Grown by Physical Vapor Deposition - Volume 9 Issue 1 - Abuhanif K. Bhuiyan, S. K. Dew, M. Stepanova