Yiu Yun Yip. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 86-87). / Yiu Yun Yip. / Contents --- p.i / List of Figures --- p.iii / List of Tables --- p.vi / Abstract --- p.vii / Acknowledgements --- p.viii / Chapter Chapter 1. --- Introduction --- p.1 / Chapter Chapter 2. --- The Fragmentation Model --- p.4 / Chapter 2.1 --- Interaction Potential --- p.5 / Chapter 2.2 --- Initial Configuration --- p.6 / Chapter 2.2.1 --- Enforcement of momentum conservation at time zero --- p.8 / Chapter 2.3 --- Time Evolution --- p.9 / Chapter 2.4 --- Summary --- p.10 / Chapter Chapter 3. --- Results for object with an initial circular shape --- p.11 / Chapter 3.1 --- Measurement of F(m) --- p.11 / Chapter 3.2 --- Results and Analysis --- p.14 / Chapter 3.3 --- Discussion --- p.24 / Chapter Chapter 4. --- Results for object with an initial square shape --- p.35 / Chapter 4.1 --- Results and Analysis --- p.35 / Chapter 4.2 --- Discussion --- p.43 / Chapter Chapter 5. --- Comparsion with experimental observations --- p.49 / Chapter 5.1 --- The Experiment --- p.49 / Chapter 5.2 --- Comparison --- p.50 / Chapter 5.2.1 --- Relation between the power-law exponent and the falling height --- p.50 / Chapter 5.2.2 --- Relation between the falling height and the total number of fragments --- p.50 / Chapter 5.2.3 --- Relation between the power-law exponent and the total num- ber of fragments --- p.53 / Chapter 5.3 --- Summary --- p.53 / Chapter Chapter 6. --- Maximum entropy formalism for fragment distributions --- p.55 / Chapter 6.1 --- The formalism --- p.55 / Chapter 6.2 --- Average potential and kinetic energies for fragments with mass m --- p.57 / Chapter 6.3 --- Comparison with simulation results --- p.67 / Chapter 6.3.1 --- Analysis for small R --- p.67 / Chapter 6.3.2 --- Analysis for large R --- p.69 / Chapter 6.4 --- Conclusion --- p.69 / Chapter Chapter 7. --- Conclusion --- p.75 / Appendix A. Main program --- p.76 / Appendix B. Derivation of P*(nm，m) and n*(m) --- p.84 / Bibliography --- p.86

Li, Hongjian. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (p. 132-156). / Abstracts in English and Chinese. / Abstract --- p.i / Abstract in Chinese --- p.iii / Acknowledgement --- p.iv / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Motivation --- p.2 / Chapter 1.2 --- Objective --- p.2 / Chapter 1.3 --- Method --- p.3 / Chapter 1.4 --- Outline --- p.4 / Chapter 2 --- Background --- p.7 / Chapter 2.1 --- Overview of the Pharmaceutical Industry --- p.7 / Chapter 2.2 --- The Process of Modern Drug Discovery --- p.10 / Chapter 2.2.1 --- Development of an Innovative Idea --- p.10 / Chapter 2.2.2 --- Establishment of a Project Team --- p.11 / Chapter 2.2.3 --- Target Identification --- p.11 / Chapter 2.2.4 --- Hit Identification --- p.12 / Chapter 2.2.5 --- Lead Identification --- p.13 / Chapter 2.2.6 --- Lead Optimization --- p.14 / Chapter 2.2.7 --- Clinical Trials --- p.14 / Chapter 2.3 --- Drug Discovery via Computational Means --- p.15 / Chapter 2.3.1 --- Structure-Based Virtual Screening --- p.16 / Chapter 2.3.2 --- Computational Synthesis of Potent Ligands --- p.20 / Chapter 2.3.3 --- General-Purpose Computing on GPU --- p.23 / Chapter 3 --- Approximate Matching of DNA Patterns --- p.26 / Chapter 3.1 --- Problem Definition --- p.27 / Chapter 3.2 --- Motivation --- p.28 / Chapter 3.3 --- Background --- p.30 / Chapter 3.4 --- Method --- p.32 / Chapter 3.4.1 --- Binary Representation --- p.32 / Chapter 3.4.2 --- Agrep Algorithm --- p.32 / Chapter 3.4.3 --- CUDA Implementation --- p.34 / Chapter 3.5 --- Experiments and Results --- p.39 / Chapter 3.6 --- Discussion --- p.44 / Chapter 3.7 --- Availability --- p.45 / Chapter 3.8 --- Conclusion --- p.47 / Chapter 4 --- Structure-Based Virtual Screening --- p.50 / Chapter 4.1 --- Problem Definition --- p.51 / Chapter 4.2 --- Motivation --- p.52 / Chapter 4.3 --- Medicinal Background --- p.52 / Chapter 4.4 --- Computational Background --- p.59 / Chapter 4.4.1 --- Scoring Function --- p.59 / Chapter 4.4.2 --- Optimization Algorithm --- p.65 / Chapter 4.5 --- Method --- p.68 / Chapter 4.5.1 --- Scoring Function --- p.69 / Chapter 4.5.2 --- Inactive Torsions --- p.72 / Chapter 4.5.3 --- Optimization Algorithm --- p.73 / Chapter 4.5.4 --- C++ Implementation Tricks --- p.74 / Chapter 4.6 --- Data --- p.75 / Chapter 4.6.1 --- Proteins --- p.75 / Chapter 4.6.2 --- Ligands --- p.76 / Chapter 4.7 --- Experiments and Results --- p.77 / Chapter 4.7.1 --- Program Validation --- p.77 / Chapter 4.7.2 --- Virtual Screening --- p.81 / Chapter 4.8 --- Discussion --- p.89 / Chapter 4.9 --- Availability --- p.90 / Chapter 4.10 --- Conclusion --- p.91 / Chapter 5 --- Computational Synthesis of Ligands --- p.92 / Chapter 5.1 --- Problem Definition --- p.93 / Chapter 5.2 --- Motivation --- p.93 / Chapter 5.3 --- Background --- p.94 / Chapter 5.4 --- Method --- p.97 / Chapter 5.4.1 --- Selection --- p.99 / Chapter 5.4.2 --- Mutation --- p.102 / Chapter 5.4.3 --- Crossover --- p.102 / Chapter 5.4.4 --- Split --- p.103 / Chapter 5.4.5 --- Merging --- p.104 / Chapter 5.4.6 --- Drug Likeness Testing --- p.104 / Chapter 5.5 --- Data --- p.105 / Chapter 5.5.1 --- Proteins --- p.105 / Chapter 5.5.2 --- Initial Ligands --- p.107 / Chapter 5.5.3 --- Fragments --- p.107 / Chapter 5.6 --- Experiments and Results --- p.109 / Chapter 5.6.1 --- Binding Conformation --- p.112 / Chapter 5.6.2 --- Free Energy and Molecule Weight --- p.115 / Chapter 5.6.3 --- Execution Time --- p.116 / Chapter 5.6.4 --- Support for Phosphorus --- p.116 / Chapter 5.7 --- Discussion --- p.120 / Chapter 5.8 --- Availability --- p.123 / Chapter 5.9 --- Conclusion --- p.123 / Chapter 5.10 --- Personal Contribution --- p.124 / Chapter 6 --- Conclusion --- p.125 / Chapter 6.1 --- Conclusion --- p.125 / Chapter 6.2 --- Future Work --- p.128 / Chapter A --- Publications --- p.130 / Chapter A.1 --- Conference Papers --- p.130 / Chapter A.2 --- Journal Papers --- p.131 / Bibliography --- p.132

This treatise is a recapitulation of the theoretical and experimental study of hysteresis in atmospheric kinetics. The original problem arose from a theoretical study of a series of reactions for clean air. Upon evaluation a bistable equilibrium was predicted. The steady-state analysis had delineated a metastable region for the set of reactions. This bounded region is the hysteresis that this research project evaluated.

The AE32000 processor core, developed by Advanced Digital Chips Inc., Korea, is used primarily in the embedded processing environment. The AE32000 simulator models this embedded processor core having high code density. An enhanced simulator was developed to study the performance of the present Instruction Set Architecture after comparison with the Simplescalar ARM simulator. ARM is among the most widely used processor cores for embedded applications and so was chosen for this comparison. Code density of the AE32000 is very high because of its shorter instruction length. This results in a smaller footprint inside the memory. But the longer instruction length of the ARM proves better when it comes to performance. The LERI(Load Extension Register Immediate) unit of the AE32000 has a special role before instructions that need long immediate values during execution. / Graduation date: 2004

This thesis presents a systematic top-down methodology for simulating a phase-locked loop using a macro model in Verilog-A. The macromodel has been used to evaluate the jitter due to supply noise, thermal noise, and ground bounce. The noise simulation with the behavioral model is roughly 310 times faster (best case) and 125 times faster (worst case). The accuracy of the model depends on the accurate evaluation of the non-linear transfer function from the various noisy nodes to the output. By modeling the noise transfer function of the circuit as closely as possible, 100% accuracy for the behavioral noise simulations compared with the HSPICE noise simulations is obtained. The macro model is written for a charge-pump phase-locked loop, but can be easily extended to other architectures. The simulations are completed using SpectreS in Cadence. The designer can use the model to estimate the jitter at the output of the PLL in a top-down design methodology or cross verify the performance of an existing chip in a bottom-up approach. / Graduation date: 2001

Graduation date: 1997

Nitrate contamination in ground and surface waters is of great concern to environmentalists. A two-dimensional model of water and solute movement in soils was used to test the usefulness and relative advantages of a two-dimensional model over a one dimensional model for analysis of deep percolation and nitrate leaching in furrow irrigation. The predictive ability of the model was evaluated using data collected in a series of preliminary field studies. Two methods were used to calibrate the model. First, the cumulative infiltration simulated by the model was compared with an infiltration curve derived from field data. Secondly, soil water potential data were used to compare the observed movement of a wetted front in the soil profile. The calibration results closely followed the two dimensional flow pattern in furrow irrigation. The model was used both in a one-dimensional mode and a two-dimensional mode. Comparison of one-dimensional and two-dimensional models was accomplished using the two-dimensional model, with uniform infiltration across the surface boundary to represent the one-dimensional case, and with infiltration only across the furrow surface for the two-dimensional case. Evaluation of water and nitrate leaching was observed for alternate furrow irrigation as well as every-furrow irrigation with three different furrow spacings; 76, 86, and 102 cm. These results showed that the one-dimensional model always under estimates the leaching amount in comparison to the two-dimensional model. In some cases the one-dimensional model predicted no leaching of water and nitrate below the root zone though leaching was predicted by the two-dimensional model. Evaluation of alternate and every furrow irrigation with different furrow spacing indicated that the leaching amount increased rapidly with the increase of furrow spacing. Under furrow irrigation, attempts to irrigate the soil profile to a level less than, but close to, field capacity will result in leaching. Therefore different irrigation management is needed to minimize leaching. Additionally, the model suggests that the sealing layer which forms in the bottom of the furrow drastically reduced the infiltration rate because of the very low saturated hydraulic conductivity in that area. Sealing layer had a significant effect on the performance of SWMS_2D model, and made the model unusable where high input volume were required. / Graduation date: 1995

Graduation date: 1995

Graduation date: 1994

Free energy simulations have been widely employed to compute the thermodynamic properties of many important biochemical processes. In the first part of this dissertation, two important biochemical processes, protonation/deprotonation of acid in solution and solvation of small organic molecules, are investigated using free energy simulations. Accurate computation of the pKa value of a compound in solution is important and challenging. To efficiently simulate the free energy change associated with the protonation/deprotonation processes in solution, a new method of mixing Hamiltonian, implemented as an approach using a fractional protonin the hybrid quantum mechanics/molecular mechanics (QM/MM) scheme, is developed. This method is a combination of a large class of λ-coupled free-energy simulation methods and the linear combination of atomic potential approach. Theoretical and technical details of this method, along with the calculation results of the pKa value of methanol and methanethiol molecules in aqueous solution, are discussed. The simulation results show satisfactory agreement with experimental data. Though the QM/MM method is one of the most useful methods in the modeling of biochemical processes, little attention has been paid to the accuracy of QM/MM methods as an integrated unit. Therefore, the solvation free energies of a set of small organic molecules are simulated as an assessment of ab initio QM/MM methods. It shows that the solvation free energy from QM/MM simulations can vary over a broad range depending on the level of QM theory / basis sets employed. Diffuse functions tend to over-stabilize the solute molecules in aqueous solution. The deviations pose a pressing challenge to the future development of new generation of MM force fields and QM/MM methods if consistency with QM methods becomes a natural requirement. In the second part of the dissertation, the dynamic and energetic properties of two molten globule (MG) protein molecules, α-lactalbumin(α-LA) and monomeric chorismate mutase (mCM) are investigated using molecular dynamics simulations. The exploring of the molecular mechanism of protein folding is a never-settled battle while the properties of MG states and their roles in protein folding become an important question. The MGs show increased side chain flexibility while maintain comparable side-chain coupling compared to the native state, which partially explains the preserving of native-like overall conformation. The enhanced sampling method, temperature-accelerated molecular dynamics (TAMD), is used for the study of the hydrophobic interactions inside both biomolecules. The results suggest that these hydrophobic cores could overcome energy barriers and repack into new conformation states with even lower energies. The repacking of the hydrophobic cores in MGs might be served as a criterion for recognizing the MGs in large class of biomolecules. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy