Submitted by Danielle Karla Martins Silva (danielle.martins@ufpe.br) on 2015-03-13T15:19:57Z No. of bitstreams: 2 TESE Victor Holanda Rusu.pdf: 9721565 bytes, checksum: 063e96f770d05cfa859b3846c87a33f5 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Made available in DSpace on 2015-03-13T15:19:57Z (GMT). No. of bitstreams: 2 TESE Victor Holanda Rusu.pdf: 9721565 bytes, checksum: 063e96f770d05cfa859b3846c87a33f5 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Previous issue date: 2014 / CAPES / Desenvolvimento de um campo de força “coarse-grain” para carboidratos. Doutorado em Química, orientador prof. Dr. Roberto Dias Lins Neto, Departamento de Química Fundamental, Universidade Federal de Pernambuco, Recife, Pernambuco, Brasil, 2014. Na natureza, os carboidratos são geralmente encontrados na forma polimérica e/ou complexados com outras biomoléculas, tais como proteínas, lipídeos, etc. A descrição teórica do comportamento destes sistemas biomoleculares requer simulações relativamente longas e consequentemente, computacionalmente custosas. Uma maneira de diminuir os requerimentos computacionais é através do uso de campos de força “coarse-grain” (CG). Nesta abordagem, grupos de átomos são mapeados em esferas diminuindo o número total de partículas no sistema, mas com o custo da perda de detalhes químicos. Neste trabalho desenvolvemos uma nova maneira de expressar carboidratos de forma mais aproximada e combinando com o modelo de água SPC CG GROMOS. O novo campo de força, denominado PITOMBA, corretamente mapeia as conformações barco e cadeira, bem como, os anômeros alfa e beta. A validação dos parâmetros são mostrados para as amilose V e A e α-, β- and γ-ciclodextrinas (CD). Nosso trabalho abre a possibilidade de simular sistemas contendo carboidratos e a termodinâmica de formação de complexos com CDs com um ganho de tempo computacional de 1-2 ordens de grandeza em comparação aos campo de força atomísticos.

Fire is the most significant natural disturbance agent in the MSdm biogeoclimatic subzone and has a determinant role in the dynamics of lodgepole pine (Pinus contorta ssp. latifolia Engelm.ex S.Wats.) dominated forests. Fire severity is a controversial term that usually refers to a qualitative measure of the fire effects on soil and vegetation and ultimately on ecosystem sustainability. The main objective of the thesis was to evaluate methods for quantifying and modelling the effects of fire severity on live biomass and dead organic matter and post-fire coarse woody debris (CWD) dynamics. A review of the representation of fire in models was conducted and several of the most commonly used fire models in North America have been described in terms of fire severity representation. The potential for developing the fire severity concept as a fire effects descriptor in an ecosystem management model were assessed. Severity matrices summarizing the probabilities of occurrence for fires of varying severity were constructed for two sites in the MSdm biogeoclimatic subzone of British Columbia, using weather data and past fire records. These matrices provide information to improve fire representation in the ecosystem based model FORECAST by quantifying the effects of fire severity on dead and live biomass components. Although this represents only a preliminary step, the severity matrix approach appears toprovide a viable methodology for improving the representation of fire effects in FORECAST. Patterns of post-fire coarse woody debris (CWD) accumulation were also assessed in the context of model development. Data were collected from a chronosequence of fire affected sites in the MSdm subzone of the TFL 49 Kelowna. The ability of the FORECAST model to simulate accumulation patterns in CWD and soil organic matter and nitrogen following fire was tested by comparing model outputs with field data. The evaluation of the model against chronosequence-derived data highlighted the fact that caution needs to be taken when using such data for model testing. The very slow recruitment pattern for new CWD illustrates the need to retain sources of CWD recruitment following fire by not salvage logging all killed trees and/or surviving live trees. / Forestry, Faculty of / Graduate

Peptide-membrane interactions play an important role in a number of biological processes, such as antimicrobial defence mechanisms, viral translocation, membrane fusion and functions ofmembrane proteins. In particular, amphipathic α-helical peptides comprise a large family of membrane-active peptides that could exhibit a broad range of biological activities. A membrane, interacting with an amphipathic α-helical peptide, may experience a number of possible structural transitions, including stretching, reorganization of lipid molecules, formation of defects, transient and stable pores, formation of vesicles, endo- and pinocytosis and other phenomena. Naturally, theoretical and experimental studies of these interactions have been an intense on-going area of research. However, complete understanding of the relationship between the structure of the peptide and themechanismof interaction it induces, as well asmolecular details of this process, still remain elusive. Lack of this knowledge is a key challenge in our efforts to elucidate some of the biological functions of membrane active peptides or to design peptides with tailored functionalities that can be exploited in drug delivery or antimicrobial strategies. In principle,molecular dynamics is a powerful research tool to study peptide-membrane interactions, which can provide a detailed description of these processes on molecular level. However, a model operating on the appropriate time and length scale is imperative in this description. In this study, we adopt a coarse-grained approach where the accessible simulation time and length scales reach microseconds and tens of nanometers, respectively. Thus, the two key objectives of this study are to validate the applicability of the adopted coarse-grained approach to the study of peptide-membrane interactions and to provide a systematic description of these interactions as a function of peptide structure and surface chemistry. We applied the adopted strategy to a range of peptide systems, whose behaviour has been well established in either experiments or detailed atomistic simulations and outlined the scope and applicability of the coarse-grained model. We generated some useful insights on the relationship between the structure of the peptides and themechanism of peptide-membrane interactions. Particularly interesting results have been obtained for LS3, a membrane spanning peptide, with a propensity to self-assembly into ion-conducting channels. Firstly, we captured, for the first time, the complete process of self-assembly of LS3 into a hexameric ion-conducting channel and explored its properties. The channel has structure of a barrel-stave pore with peptides aligned along the lipid tails. However, we discovered that a shorter version of the peptide leads to a more disordered, less stable structure often classified as a toroidal pore. This link between two types of pores has been established for the first time and opens interesting opportunities in tuning peptide structures for a particular pore-inducing mechanism. We also established that different classes of peptides can be uniquely characterized by the distinct energy profile as they cross the membrane. Finally, we extended this investigation to the internalization mechanisms of more complex entities such as peptide complexes and nanoparticles. Coarse-grained steered molecular dynamics simulations of these model systems are performed and some preliminary results are presented in this thesis. To summarize, in this thesis, we demonstrate that coarse-grained models can be successfully used to underpin peptide interaction and self-assembly processes in the presence of membranes in their full complexity. We believe that these simulations can be used to guide the design of peptides with tailored functionalities for applications such as drug delivery vectors and antimicrobial systems. This study also suggests that coarse-grained simulations can be used as an efficient way to generate initial configurations for more detailed atomistic simulations. These multiscale simulation ideas will be a natural future extension of this work.

Coarse-graining and multi-scale approaches are rapidly becoming important tools for computer simulations of large complex molecular systems. Such theoretical models are powerful tools because they allow one to probe the essential features of a complex, many-bodied system on length and time scales over which emergent phenomena may occur. Because of the computational advantages and fundamental insight made available through coarse-grained methods, a vast array of various phenomenological potentials to describe coarse-grained interactions have been developed; nonetheless, the ability of these potentials to provide quantitative information about several different properties of the same system is not evident. On a theoretical level, it is not well-understood how small correlations in the long-range structure propagate through the coarse-graining procedure into the effective potential and lead to incorrect thermodynamics. Taking an alternative approach, this dissertation will discuss an analytical coarse-graining method for synthetic polymer chains of specific chemical structure, where a group of atoms on a polymer chain are represented by a variable number of soft interacting effective sites. The approach is based in liquid-state theory, providing a theoretical framework to address questions of thermodynamic consistency. It will be shown that the proposed method of coarse-graining maintains thermodynamic consistency for a variety of polymer models. In a multi-scale modeling scheme simulations of the same system represented by several different levels of detail may be joined to provide a complete description of the system at all length and time scales of interest. This dissertation includes previously published and unpublished co-authored material.

An antibody microarray consists of antibody bound to a surface. Antibody microarrays have great potential in many fields, particularly as a tool to detect antigens. Unfortunately, antibodies suffer from poor performance. A greater understanding of how antibodies interact with surfaces would improve microarray design and performance, but experimental methods fall short of being able to observe these interactions. Therefore molecular simulation has emerged as the primary method to study protein/surface interactions.The simulations here were coarse grain simulations performed using the model of Karanicolas and Brooks. Additionally, an advanced surface model was used that allows for different surface chemistries. PyMBAR analysis was used to find heat capacities and determine relative stabilities of different linkers and tethering sites for the antibody/surface system.The actual work looked at how 24 different tethering sites affect antibody stability on two different surfaces and examined nine linkers varying in length and rigidity. Ultimately the findings were that antibody stability is a function of tethering position when tethered to a hydrophobic surface, but not when tethered to a hydrophilic surface. Furthermore, the length and rigidity of the linkers do not have a significant impact on stability.

Configurable devices have become more and more popularnowadays. This is because they can improve the system performance inmany ways. In this thesis work it is studied how introduction of coarse grain configurability can improve the ePUMA, the low power highspeed DSP platform, in terms ofperformance and power consumption. This study takes two DSP algorithms, Fast Fourier Transform (FFT) and FIR filtering asbenchmarks to study the effect of this new feature. Architectures are presented for calculation of FFT and FIR filters and it is shown how they can contribute to the system performance. Finally it is suggestedto consider coarse grain configurability as an option for improvement of the system.

Thesis (M.S.)--Humboldt State University, 2009. / Includes bibliographical references (leaves 71-82). Also available via Humboldt Digital Scholar.

Thesis (Ph. D.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains viii, 198 p. : ill., maps. Vita. Includes abstract. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 70-77).

It is common for field models of tight gas reservoirs to include several wells with hydraulic fractures. These hydraulic fractures can be very long, extending for more than a thousand feet. A hydraulic fracture width is usually no more than about 0.02 ft. The combination of the above factors leads to the conclusion that there is a need to model hydraulic fractures in coarse grid blocks for these field models since it may be impractical to simulate these models using fine grids. In this dissertation, a method was developed to simulate a reservoir model with a single hydraulic fracture that passes through several coarse gridblocks. This method was tested and a numerical error was quantified that occurs at early time due to the use of coarse grid blocks. In addition, in this work, rules were developed and tested on using uniform fine grids to simulate a reservoir model with a single hydraulic fracture. Results were compared with the results from simulations using non-uniform fine grids.