Computational Chemistry Commons^™

Modeling Sex-Specific Changes In Myocardial Fibrosis, Grace Martin

Chemical Engineering Undergraduate Honors Theses

Heart disease the leading cause of death for both men and women in the United States. Cardiac fibrosis, or accumulation of extracellular matrix proteins in the heart, can occur after a heart attack and increase the risk for further complications. Current treatments for heart disease do not include extracellular matrix regulators, partly due to the complicated signaling network responsible for the production of these proteins. By using a computational model of the signaling network in cardia fibroblasts, the relationship between particular molecules and downstream extracellular matrix production can be examined.

Biological sex is an important factor for cardiac health and …

Design, Synthesis, And Optimization Of Allosteric Inhibitors Of Hiv-1 Integrase, Krunal H. Patel

Dissertations

The human immunodeficiency virus type 1 (HIV-1) infection remains a global health crisis, necessitating the development of innovative antiviral strategies. During the integration step, HIV-1 integrase (IN) interacts with viral DNA and the cellular cofactor LEDGF/p75 to effectively integrate the reverse transcript into the host chromatin. Recently, a novel class of antiretroviral agents called Allosteric Inhibitors of HIV-1 Integrase (ALLINI) compounds has emerged as a promising avenue in the fight against HIV-1. While originally designed to inhibit IN-LEDGF/p75 interactions, these compounds have been shown to also impact late-stage viral maturation severely through IN multimerization. Induction of IN multimerization interferes with …

Computational Study Of Fluorescent Molecular Probes For The Early Detection Of Alzheimer's Disease, Gabriela Elizabeth Molina Aguirre

Open Access Theses & Dissertations

Alzheimer's disease is a debilitating brain disorder that affects memory, thinking, and behavior. It is the most prevalent form of dementia and the seventh leading cause of death in the United States. As, researchers have identified biomarkers that can indicate the presence of the disease many years before the first symptoms appear, so there is an opportunity for early detection and treatment follow-ups, which could significantly improve the quality of life for those affected by this disease.This dissertation investigates the relationship between molecular structure and optical properties of donor-bridge-acceptor (DBA) fluorescent molecular probes designed for detecting Amyloid-β and p-Tau protein …

Computational Investigation Of Transition Metal Photoredox Catalysis: Redox Property Tuning Via Ligand Modification, Christian Fernando Sandoval Pauker

Open Access Theses & Dissertations

In the last decade, photoredox catalysis has become a powerful tool in synthetic chemistry. It relies on the ability of catalytic systems that facilitate energy-demanding redox reactions thanks to photoinduced electron transfer processes. This dissertation focuses on the computational investigation of the redox properties of transition metal photoredox catalysts using density functional theory (DFT) calculations. The research systematically explores the effects of altering redox-active ligands on the thermodynamics of electron transfer events in the photoredox cycle. The electronic structure changes throughout oxidative and reductive quenching cycles are analyzed, with a particular focus on Cu(I) complexes. Through computational techniques, insights into …

Design And Application Of Smart Systems To Address Analytical Problems, Lucas B. Ayres

All Dissertations

This dissertation is a multidisciplinary effort that integrates low-cost analytical instrumentation, redox chemistry, and artificial intelligence to overcome existing limitations in the fields of wearable sensing technology, Deep Eutectic Solvents (DES), and antioxidant chemistry. The overall goal behind each implemented strategy is to enhance the accuracy, efficiency, and accessibility of analytical processes and technologies. A general overview of the thesis, along with the research outcomes is included in Chapter One. The theoretical framework of this dissertation is presented in Chapter Two. Chapter Three describes the development of a wearable platform (sensor and instrumentation) to rapidly detect (~20 minutes) S. aureus …

Modelling Terrestrial And Potential Extraterrestrial Photopigments Via Density Functional Theory, Dorothea Illner

Theses and Dissertations

In the search for extraterrestrial life, biosignatures play a crucial role in identifying its putative traces. A commonly known and robust biosignature is the Vegetation Red Edge (VRE), which can be described as a sharp increase of reflectance observed from a planet and stems from the light absorption of photopigments in specific regions in the electromagnetic spectrum. For Earth, this VRE is known to occur around 700 nm, however, if the photopigments absorb light in different regions and have different structures the VRE could experience a wavelenght shift.

In this work, Chlorophyll a and a potential photopigment precursor called Phot0 …

Methods For Computing Rovibrational Spectral Data With Applications To Inorganic Oxides And Hydrocarbons, Alexandria Watrous

Honors Theses

Computational chemistry focuses on finding solutions to the time-independent Schrödinger equation for systems of interest to study their molecular properties such as rovibrational spectral data. Any molecule containing more than one electron cannot be solved explicitly but coupled cluster theory offers one of the best approximations. One such application of this method is to molecules of astrochemical interest to support observation and experimental data. Chapters 2, 3, and 4 look at the performance of new couple cluster theory methods including composite and hybrid methods for ground and excited state rovibrational data. Chapters 5 - 9 use the previously mentioned methods …

Unlocking The Secret To Weight Loss: Discovering The Most Effective Green Tea Products, Seoyeon Kim

SACAD: Scholarly Activities

To find the most effective green tea product that can replace

weight loss drugs, we compared the amount of catechin in six

different green tea products. The result was green tea latte

powder contained a significantly small amount of catechin

compared to other products, and the dried pearl green tea leaves

had the highest amount of catechin. Also, the unexpected result

was that green tea supplements had less amount of catechin

compared to dried leaves or even tea bags that are commonly

sold in markets.

Decoding Molecular Recognition Mechanism Of Small Molecule Ligand-Rna Binding Pocket Systems Using Molecular Dynamics And Metadynamics, Zhixue Bai

Legacy Theses & Dissertations (2009 - 2024)

From my PhD research, under Amber99-Chen-Garcia force field, umbrella sampling and MD simulation helped us found that the 2’-5’ phosphodiester RNA backbone linkage modification on in vitro selected neomycin RNA aptamer can transfer it to ‘amikacin RNA aptamer’ by changing the conformation and backbone rigidity of the RNA binding pocket, which further influenced the binding mode and binding pathway of amikacin. Furthermore, under the same force field, metadynamics was found more powerful for simulating the binding pathway, binding mechanism and predicting binding modes of small molecule ligand recognizing its RNA target by filling up all energy basins on free energy …

Development Of On-The-Fly Quasi-Steady State Approximation For Chemical Kinetics In Cfd, Abhinav Balamurugan

Doctoral Dissertations and Master's Theses

This study analyzes the feasibility of On-The-Fly Quasi-Steady-State Approximation (OTF-QSSA) application for solving chemical kinetics within Computational Fluid Dynamics (CFD) simulations, aiming to reduce the computational demand of detailed mechanisms. An algorithm that dynamically identifies and designates Quasi-Steady-State (QSS) species at specific grid locations and instances during the simulation was developed. With this information, our method pseudo-delays the advancement of concentrations for these QSS species—effectively setting their rate of concentration change to zero for a set number iteration before updating using the detailed mechanism and thereby omitting the computationally intensive processes typically required for their calculation during those skipped iteration. …

Accurate Characterization Of Binding Kinetics And Allosteric Mechanisms For The Hsp90 Chaperone Inhibitors Using Ai-Augmented Integrative Biophysical Studies, Chao Xu, Xianglei Zhang, Lianghao Zhao, Gennady M. Verkhivker, Fang Bai

Mathematics, Physics, and Computer Science Faculty Articles and Research

The binding kinetics of drugs to their targets are gradually being recognized as a crucial indicator of the efficacy of drugs in vivo, leading to the development of various computational methods for predicting the binding kinetics in recent years. However, compared with the prediction of binding affinity, the underlying structure and dynamic determinants of binding kinetics are more complicated. Efficient and accurate methods for predicting binding kinetics are still lacking. In this study, quantitative structure–kinetics relationship (QSKR) models were developed using 132 inhibitors targeting the ATP binding domain of heat shock protein 90α (HSP90α) to predict the dissociation rate …

In Silico Analysis Of C-Type Lectins As Co-Infection Receptors Of Dengue And Chikungunya Viruses In Aedes Aegypti, Munawir Sazali, R. C. Hidayat Soesilohadi, Nastiti Wijayanti, Tri Wibawa, Arif Nur Muhammad Ansori

Makara Journal of Science

Aedes aegypti is a primer vector of dengue virus (DENV) and chikungunya virus (CHIKV). The susceptibility of mosquitoes to DENV and CHIKV depends on their recognition receptor of pathogens. C-type lectins (CTLs) are an important mediator of virus infection in A. aegypti. This study aims to identify potential receptors and determine the binding affinity between ligand–receptor interaction, CTLs and virus envelopes (DENV-1, 2, 3, and 4 and CHIKV) interaction based on in silico analysis. Sample sequences were obtained from GenBank (NCBI), and 10 CTLs were acquired from VectorBase. Homology modeling based on a minimum standard of 20% was processed …

Mechanistic Investigation Of C—C Bond Activation Of Phosphaalkynes With Pt(0) Complexes, Roberto M. Escobar, Abdurrahman C. Ateşin, Christian Müller, William D. Jones, Tülay Ateşin

Research Symposium

Carbon–carbon (C–C) bond activation has gained increased attention as a direct method for the synthesis of pharmaceuticals. Due to the thermodynamic stability and kinetic inaccessibility of the C–C bonds, however, activation of C–C bonds by homogeneous transition-metal catalysts under mild homogeneous conditions is still a challenge. Most of the systems in which the activation occurs either have aromatization or relief of ring strain as the primary driving force. The activation of unstrained C–C bonds of phosphaalkynes does not have this advantage. This study employs Density Functional Theory (DFT) calculations to elucidate Pt(0)-mediated C–CP bond activation mechanisms in phosphaalkynes. Investigating the …

Β-Sheets Mediate The Conformational Change And Allosteric Signal Transmission Between The Aslov2 Termini, Sian Xiao, Mayar Terek Ibrahim, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

Avena sativa phototropin 1 light-oxygen-voltage 2 domain (AsLOV2) is a model protein of Per-Arnt-Sim (PAS) superfamily, characterized by conformational changes in response to external environmental stimuli. This conformational change begins with the unfolding of the N-terminal A'α helix in the dark state followed by the unfolding of the C-terminal Jα helix. The light state is characterized by the unfolded termini and the subsequent modifications in hydrogen bond patterns. In this photoreceptor, β-sheets are identified as crucial components for mediating allosteric signal transmission between the two termini. Through combined experimental and computational investigations, the Hβ …

Investigating The Structural Ensemble And Dynamic Interactions Of Protein Interacting With C-Kinase 1 (Pick1) Using Computational Tools, Amy E. Stevens

Chemistry and Chemical Biology ETDs

Protein Interacting with C Kinase-1 (PICK1) is a scaffolding protein that offers a promising solution to support individuals suffering from substance use disorders. While many efforts have been put towards identifying small-molecule drugs with the potential to target PICK1 and ultimately support individuals suffering from the effects of substance use disorders, all efforts have so far fallen short. The purpose of this work is to use computational tools to assist the design of a small-molecule inhibitor of PICK1 while also advancing the knowledge of its biological functions. This work provides information that is currently missing the field by (1) revealing …

Automated Workflow For Redox Potentials And Acidity Constants Calculations From Machine Learning Molecular Dynamics, Feng Wang, Jun Cheng

Journal of Electrochemistry

Redox potentials and acidity constants are key properties for evaluating the performance of energy materials. To achieve computational design of new generation of energy materials with higher performances, computing redox potentials and acidity constants with computational chemistry have attracted lots of attention. However, many works are done by using implicit solvation models, which is difficult to be applied to complex solvation environments due to hard parameterization. Recently, ab initio molecular dynamics (AIMD) has been applied to investigate real electrolytes with complex solvation. Furthermore, AIMD based free energy calculation methods have been established to calculate these physical chemical properties accurately. However, …

Measurements Of Rate Constant For Electrode Reactions, Lian-Huan Han, Jia-Yao Guo, Miao-Miao Cui

Journal of Electrochemistry

Standard electron-transfer rate constant is one of the intrinsic properties for an electrochemical reaction, which is significant in the study of electrode kinetics. It is a key criterion for one to clarify the mechanism and pathway of a specific electrochemical reaction, and to screening and design the electrocatalysts and battery materials. Herein, we will introduce the measuring methods of rate constant for electrode reactions, including polarization curve, rotating disk electrode, ultramicroelectrode, scanning electrochemical microscopy, electrochemical impedance spectroscopy, current step, potential step and cyclic voltammetry, etc., to provide a guide to investigate electrode kinetics for graduate students and researchers in the …

Confirmation Of Anomalous-Heat Report, Steven B. Krivit, Melvin H. Miles

Journal of Electrochemistry

This study identifies, for the first time, critical calculation errors made by Nathan Lewis and his co-authors, in their study presented on May 1, 1989, at the American Physical Society meeting in Baltimore, Maryland. Lewis et al. analysed calorimetrically measured heat results in nine experiments reported by Martin Fleischmann and his co-authors. According to the Lewis et al. analysis, each of the experiments, where calculated for no recombination, showed anomalous power losses. When we used the same raw data, our corrected calculations indicate that each experiment showed anomalous power gains. As such, these data suggest the possibility of a new, …

Joint Time-Frequency Analysis: Taking Charge Penetration Depth And Current Spatial Distribution In The Single Pore As An Example, Nan Wang, Qiu-An Huang, Wei-Heng Li, Yu-Xuan Bai, Jiu-Jun Zhang

Journal of Electrochemistry

In recent years, joint time-frequency analysis has once again become a research hotspot. Supercapacitors have high power density and long service life, however, in order to balance between power density and energy density, two key factors need to be considered: (i) the specific surface area of the porous matrix; (ii) the electrolyte accessibility to the intra-pore space of porous carbon matrix. Electrochemical impedance spectra are extensively used to investigate charge penetration ratio and charge storage mechanism in the porous electrode for capacitance energy storage. Furthermore, similar results could be obtained by different methods such as stable-state analysis in the frequency …

Evaluating The Reliability And Accuracy Of Alchemical Binding Free Energy Methods And Calculations, Fnu Sheenam

Dissertations, Theses, and Capstone Projects

Molecular recognition plays a crucial role in various biological processes, such as enzymatic reactions, signal transduction, and genetic information processing. Investigating how proteins selectively bind to their partners is an active research area, but there is a lack of experimental details on protein structures and interactions in molecular complexes. Computational techniques based on macromolecular structures offer a way to predict protein-ligand interactions and explore their recognition mechanisms. Estimating binding affinities, particularly through alchemical binding free energy calculations, has become valuable in supporting drug discovery. This work introduces new methodologies, utilizing the Alchemical Transfer Method, to address issues like poor convergence …