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CHEMISTRY OF BUCKYBOWL FROM CLOSED-SHELL TO OPEN-SHELL
Title
CHEMISTRY OF BUCKYBOWL FROM CLOSED-SHELL TO OPEN-SHELL
Creator
Li, Jingbai
Date
2019
Description
Buckybowl is an open geodesic polyaromatic molecule with unevenly distributed π-electron on its convex and concave surface, which leads to a...
Show moreBuckybowl is an open geodesic polyaromatic molecule with unevenly distributed π-electron on its convex and concave surface, which leads to a readily accessible π-surface for substitution reactions and complexation with various metals. Despite the diverse structures of buckybowl complexes observed in the previous experimental study, our computational work has shown that the π-surface of buckybowl always plays the most important role in the bonding. Modification of the π-surface by changing the size of conjugation and the curvature enable us to tune the bonding preference of the buckybowl surface and the stability of the complex. Our continued study has shown similar importance of the π-surface in functionalization of buckybowl with different electrophilic groups. Surprisingly, our investigation on buckybowl cations intrigued an original perspective of aromatic behavior of the π-surface. Our results have revealed an intrinsic nature of aromatic stabilization in polyaromatic cations, which is mainly attributed to the depletion of anti-aromaticity at the center ring. Further study showed an explicit correlation between the curvature of π-surface and the stability of adducts, aromatic behavior at center ring, as well as the spin distribution over polyaromatic moiety. By curving the π-surface, we have proposed several buckybowl radical adducts and confirmed their stability. These models provide an alternative strategy of developing polyaromatic spin carriers, which have a great potential in the manufacture of quantum bits. We believe our comprehensive theoretical study on versatile chemistry of buckybowl and related polyaromatic hydrocarbons can offer fundamental understanding and essential guidance for developing buckybowl-based electrode materials in the lithium-ion battery, organometallic building block, and spin electronic devices.
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Implicit ligand theory: binding free energy calculations based on multiple rigid receptor snapshots
Title
Implicit ligand theory: binding free energy calculations based on multiple rigid receptor snapshots
Creator
Xie, Bing
Date
2018
Description
Binding affinity plays an important role in drug design. Accurate and fast prediction of binding free energies remains a major challenge for...
Show moreBinding affinity plays an important role in drug design. Accurate and fast prediction of binding free energies remains a major challenge for structure-based calculation. We have developed a fast free energy calculation program AlGDock and applied it to different systems. In this thesis, I will first demonstrate the feasibility of estimating protein-ligand binding free energies using multiple rigid receptor configurations on T4 lysozyme. Based on 576 snapshots extracted from six alchemical binding free energy calculations with a flexible receptor, binding free energies were estimated for a total of 141 ligands. For 24 ligands, the calculations reproduced flexible-receptor estimates with a correlation coefficient of 0.90 and a root mean square error of 1.59 kcal/mol. The accuracy of calculations based on Poisson-Boltzmann/Surface Area implicit solvent was comparable to previously reported free energy calculations. Then we evaluate a number of common snapshot selection strategies using a quality metric from stratified sampling, the efficiency of stratification, which compares the variance of a selection strategy to simple random sampling. For docking sets of over five hundred ligands to four different proteins of varying flexibility, we observe that for estimating ensemble averages and exponential averages, many clustering algorithms have similar performance trends: for few snapshots (less than 25), medoids are the most efficient while for a larger number, optimal (the allocation that minimizes the variance) and proportional(to the size of each cluster) allocation become more efficient. Proportional allocation appears to be the most consistently efficient for estimating minima. Finally, we attempted a blinded prediction challenge D3R and applied AlGDock on several systems. I will describe the performance of our calculation. Overall, the study shows that AlGDock can work well for predicting the binding affinities and it demonstrates a strategy for developing an understanding of protein-ligand interactions.
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Computational study on the heme scavenging ability of Staphylococcus aureus IsdH receptor: Utilizing molecular dynamics to understand an unknown mechanism
Title
Computational study on the heme scavenging ability of Staphylococcus aureus IsdH receptor: Utilizing molecular dynamics to understand an unknown mechanism
Creator
Clayton, Joseph Alan
Date
2021
Description
Methicillin-resistant Staphylococcus aureus (MRSA) has become an infamous pathogen with infection rates that have declined slowly in recent...
Show moreMethicillin-resistant Staphylococcus aureus (MRSA) has become an infamous pathogen with infection rates that have declined slowly in recent years. S. aureus requires iron as a metabolic nutrient during infection and obtains this nutrient through an iron-regulated surface-determinant (Isd) system that extracts iron from the host’s heme stored in hemoglobin (Hb) through near iron transporter (NEAT) domains. This work concentrates on studying the second and third NEAT domains of IsdH by utilizing atomistic molecular dynamics to probe the heme scavenging process; in collaboration with the Clubb Group at UCLA, we discover key functional regions of IsdH and describe fundamental interdomain dynamics. In addition, I investigate a conventional computational method to describe protein dynamics and propose an alternative that aims to alleviate computational effort by incorporating experimental data.
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THE INTERACTION BETWEEN COINAGE OR ALKALI METALS AND POLYAROMATIC HYDROCARBONS
Title
THE INTERACTION BETWEEN COINAGE OR ALKALI METALS AND POLYAROMATIC HYDROCARBONS
Creator
Liu, Shuyang
Date
2020
Description
Theoretical study on versatile chemistry of buckybowls and related polyaromatic hydrocarbons has been comprehensively accomplished and...
Show moreTheoretical study on versatile chemistry of buckybowls and related polyaromatic hydrocarbons has been comprehensively accomplished and documented. Polyaromatic hydrocarbons from simple double bond to fullerene C60, as one of major family in buckybowls has shown a wide potential in development of various specifically purposed materials. Complexes with coinage metals evidenced tunable donor ability of related polyaromatic systems’ π-surface. Moreover, functionalization with small ligands cations interact with these π-surface also show some patterns which have certain enlightenment to the experiment. By adding the methyl group on corannulene, to pursue the relationship between geometry and stabilization which provide an alternative strategy of developing. Further study of alkali metals interacts with annulene, continuously adding with crown ether to mimic experiment environment display an interesting pattern. In the end, extended topics of some applications with computational chemistry, such as the help of Raman spectrum of L-focus.
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USING COMPUTATIONAL MOLECULAR MODELING TO STUDY TRANSPORT PROCESSES OF INTEREST IN SEPARATIONS
Title
USING COMPUTATIONAL MOLECULAR MODELING TO STUDY TRANSPORT PROCESSES OF INTEREST IN SEPARATIONS
Creator
Wang, Xiaoyu
Date
2020
Description
Separation processes are widely used in chemical productions. The further development of membrane-based separation processes, compared with...
Show moreSeparation processes are widely used in chemical productions. The further development of membrane-based separation processes, compared with thermal separations, can lead to significant energy savings in chemical process industries. However, the main obstacle of experiments is that many separation processes are not well understood at the fundamental molecular level. In this dissertation, we use computational molecular modeling tools, mainly classical molecular dynamics (MD), to clarify molecular forces and provide detail at a molecular level, which can aid in the understanding of transport process and designing materials for a proposed application.In the first study, we investigated separation of water/alcohol vapor using zeolite membranes. Experimentally, the separation of water/isopropanol (IPA) mixtures shows a dramatic decrease in selectivity due to increase of IPA flux as the feed water concentration decrease when using the sodium A zeolite membrane. We used molecular dynamics simulations to help our experimental collaborators understand these puzzling results. The MD results reveal that the water molecules gather around the defect pores on the zeolite membrane, which stops the IPA from going through the membrane and has a positive effect on separation.Then, we studied the HPLC used to separate chiral drug mixtures. One popular chiral stationary phase, amylose tris(3,5-dimethylphenyl carbamate) (ADMPC), has been investigated using both experimental and computational methods; however, the dynamic nature of the interaction between enantiomers and ADMPC, as well as the solvent effects on the ADMPC-enantiomer interaction, are currently absent from the chiral recognition mechanism. We used MD simulations to model the ADMPC in different solvents to elucidate the chiral recognition mechanism from a new dynamic perspective. The ADMPC is found to hold the left-handed helical structure in both methanol and heptane/IPA (90/10); however, the ADMPC has a more extended average structure in heptane/IPA. We developed a model where the ADMPC atoms were restricted in the MD simulation. To better understand the molecular dynamic chiral recognition that provides the retention factor and the elution order in HPLC, we examined hydrogen bonding lifetimes, and mapped out ring-ring interactions between the drugs and the ADMPC. We discover several MD metrics related to hydrogen-bonding lifetimes and correlate them with HPLC results. One metric provides a prediction of the correct elution order 90%, and the ratios of these quantities for the enantiomers provide linear correlation (0.85 coefficient) with experimental retention factors.In the following study, we presented an improved model wherein multiple ADMPC polymer strands are coated on an amorphous silica slab. Using various MD techniques, we successfully coated ADMPCs onto the surface without losing the structural character of the backbone in the solvent. This model provides more opportunities for chiral molecules interacting with ADMPC, resulting in a better agreement compared with experiment when using the overall average metric. The new model also provides the possibility for drug molecules to interact with two polymer strands simultaneously, which is not possible in the previous single-strand model. For a better understanding of why some metrics are better predictors than others, we used charts of the distribution of hydrogen bonding lifetimes to display the information for various donor-acceptor pairs. The results are more consistent than the previous models and resolves the problematic cases of thalidomide and valsartan.Besides the membrane-based separations, immiscible liquid-liquid equilibrium states were also studied. We successfully predicted results based on MD simulations and showed comparable accuracy with experimental data. This method has applications in liquid-liquid extraction which is widely used in industrial separation process.
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