Browsing by Subject "Molecular dynamics simulation"

Now showing 1 - 4 of 4
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    Application of Improved Aerosol Deposition to Deposit Functional Films and Atomistic Investigation of Dynamic Response of Particle During Ballistic Impact
    (2023-01) Song, Guanyu
    Aerosol deposition (AD) is a novel approach to producing robust nanocrystalline thin films or thick ceramic coatings at room temperature. It is hence applicable to variable substrates from low-melting metal substrates to refractory ceramic substrates. Aerosolizing precursor powder into appropriate size distribution and concentration is crucial to making films with good adhesion. The fluidized bed is a common approach, which is driven by a pressure difference for aerosol generation. Nonetheless, this method often fails to make aerosol flow with proper size distribution without pre-treatment on precursor powder.Furthermore, owing to its solid-state deposition property, particle-substrate interaction plays an essential role in AD, especially in making thin films with nanoparticles. Numerous experimental and simulation studies have been investigated to physically and theoretically understand events of particle-substrate interaction in AD. However, thermal energy evolution and structural transformation in nanoparticles have so far not been fully elucidated. Therefore, the purpose of the studies proposed here is to develop different methods for generating aerosol flow, subject to the type of as-deposited coatings, and to perform simulation studies focusing on nanoparticle-substrate interaction at an atomistic scale. The first portion of my dissertation will focus on combining the spray pyrolysis technique with aerosol deposition (AD) for producing Yttria-stabilized zirconia (YSZ) based thermal barrier coatings (TBCs). The desired outcome of this study is to achieve an in-flight synthesis of applied particles in AD and deposit synthesized YSZ particles into layers. We additionally investigate the effect of operating conditions of spray pyrolysis on the size distribution of synthesized particles, the impact of substrate hardness on the coatings growth rate, and the influence of solute composition in precursor liquid on the thermal performance of as-deposited YSZ coatings. The second portion of my dissertation will develop a voice-coil-based powder dispensing system for aerosol generation, coupling it with conventional aerosol deposition (AD) and co-deposit thermoelectric coatings with variable elements ratio by this improved AD setup. Transport properties of as-deposited samples with different amounts of the doped element will be measured to know the dopant effect on the thermoelectric performance of as-deposited coatings. The third portion of my dissertation will focus on elucidating nanoparticle-substrate interaction in aerosol deposition at an atomistic scale via molecular dynamics (MD) simulations. Yttria-stabilized zirconia (YSZ) is selected as the material for both impacting nanoparticles and substrates. The simulations that will be performed can be categorized into cold impact and thermal impaction simulations. In cold impact simulations, we will study the influence of impact speeds on thermal energy evolution, structural transformation, and mechanical deformation in nanoparticles and substrates. In thermal impact simulations, we will investigate the role that ratio of translational kinetic energy and thermal energy in nanoparticles plays and demonstrate the influence of this ratio on nanoparticle behavior during the collision process. The final section of my dissertation focuses on investigating the effects of particle grain size on its plasticity, deformation mechanism, and dislocation propagation during the ballistic impact. By using molecular dynamics simulation, we can study the microstructure transformation and dislocation interactions in the particle over the compressive strains. The results indicate that impact velocity adversely affects the dislocation mobility in the particle, and there is increased dislocation density in the particle with a larger initial grain size.
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    Assessment and Improvement of Computational Models to Study Biological Catalysis
    (2014-08) Huang, Ming
    A detailed understanding of the molecular mechanisms whereby molecules of RNA can catalyze important reactions such as phosphoryl transfer is fundamental to biology, and of high significance in the development of new biomedical technology. This thesis describes the testing, application and development of quantum models that advance our understanding of the mechanisms of RNA catalysis. Molecular simulations of catalytic mechanisms of RNA require the use of fast, accurate approximate quantum mechanical (QM) models. These models, however, were not necessarily designed and parameterized for biocatalysis. In order to assess the degree to which commonly used approximate QM models are appropriate for biocatalysis applications, a series of models has been tested against a wide range of data sets, including new datasets particularly relevant for RNA catalysis, and compared with high-level benchmark calculations. Results provide new insight into the strengths and weaknesses of these methods, and help to guide next generation model development. We note that both NDDO and SCC-DFTB based QM models fail dramatically in their ability to adequately describe the conformational landscape of DNA and RNA sugar rings. In order to overcome this problem, an empirical sugar pucker energy term has been introduced via multi-dimensional B-spline interpolation of a potential energy surface correction. The corrected semiempirical models closely reproduce the ab initio puckering profiles as well as the barrier of an RNA transesterification model reaction. In addition, a series of RNA transesterification model reactions with various leaving groups have been studied with density-functional calculations in solution to investigate linear free energy relationships (LFERs) and their connection to transition state structure and bonding. These relations can be used to aid in the interpretation of experimental data for non-catalytic and catalytic mechanisms. A driving force in this research has been the development of software infrastructure for scientific computation, including new interfaces to other computational chemistry software, libraries to retrieve information, convert format and apply potentials, and tools for data analysis and visualization.
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    Computer Simulations and Experimental Designs to Study the Mechanisms of Actions of Antimicrobial Peptides
    (2018-10) Lai, Pin-Kuang
    Antimicrobial peptides (AMPs) are promising alternatives to traditional antibiotics, which have a serious resistance crisis. We studied the mechanisms of three different types of AMPs using computational and experimental methods. First, computer simulations are performed to study the AMP microcin J25 (MJ25), a 21-mer peptide with an unusual lasso structure and high activity against Gram-negative bacteria. MJ25 has intracellular targets. The initial step for MJ25 acquisition in bacterial cells is binding to the outer membrane receptor FhuA. Molecular dynamics simulation is implemented to study the binding mechanism of MJ25 to FhuA and to search for important binding residues. The absolute binding free energy calculated from combined free energy perturbation (FEP) and thermodynamic integration (TI) methods agrees well with experimental data. In addition, computational mutation analysis reveals that the His5 is the key residue responsible for MJ25 and FhuA association. We find that the number of hydrogen bonds is essential for MJ25 binding to FhuA. This atomistic, quantitative insight sheds light on the mechanism of action of MJ25, and may pave a path for designing active MJ25 analogues. Second, protegrin-1 (PG-1) is a cationic arginine-rich AMP. It is widely accepted that PG-1 induces membrane disruption by forming pores that lead to cell death. However, the insertion mechanism for these highly cationic peptides into the hydrophobic membrane environment is still poorly understood at the molecular scale. It has previously been determined that the association of arginine guanidinium and lipid phosphate groups results in strong bidentate bonds that stabilize peptide-lipid complexes. It has also been suggested that arginine residues are able to drag phosphate groups as they insert inside the membrane to form a toroidal pore. However, whether bidentate bonds play a significant role in inducing a pore formation remains unclear. To investigate the role of bidentate complexes in PG-1 translocation, we conducted molecular dynamics simulations. Two computational electroporation methods were implemented to examine the translocation process. We found PG-1 could insert into the membrane provided the external electric potential is large enough to first induce a water column or pore within the lipid bilayer membrane. We also found that the highly charged PG-1 is capable in itself of inducing molecular electroporation. Substitution of arginines with charge-equivalent lysines showed a markedly reduced tendency for insertion. This indicates the guanidinium group likely facilitates PG-1 translocation. Potential of mean force calculations suggest that peptide insertion inside the hydrophobic environment of the membrane core is not favored. We found that formation of a water column or pore might be a prerequisite for PG-1 translocation. We also found PG-1 can stabilize the pore after insertion. We suggest that PG-1 could be a pore inducer and stabilizer. This work sheds some light on PG-1 translocation mechanisms at the molecular level. Methods presented in this study may be extended to other arginine-rich antimicrobial and cell-penetrating peptides. Third, oncocin is a proline-rich antimicrobial peptide that inhibits protein synthesis by binding to the bacterial ribosome. In this work, the antimicrobial activity of oncocin was improved by systematic peptide mutagenesis and activity evaluation. We found that a pair of cationic substitutions (P4K and L7K/R) improves the activity by 2-4 fold (p<0.05) against multiple Gram-negative bacteria. An in vitro transcription / translation assay indicated that the increased activity was not because of stronger ribosome binding. Rather a cellular internalization assay revealed a higher internalization rate for the optimized analogs thereby suggesting a mechanism to increase potency. In addition, we found that the optimized peptides’ benefit is dependent upon nutrient depleted media conditions. The molecular design and characterization strategies have broad potential for development of antimicrobial peptides.
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    The solution of the boundary-value problems for the simulation of transition of protein conformation
    (University of Minnesota. Institute for Mathematics and Its Applications, 2008-03) Vedell, Peter; Wu, Zhijun