Computational Chemistry Commons^™

Exploring Ancestral Enzymes Through Sequence Reconstruction And Stability Prediction, Jeyun Park, Masakatsu Watanabe

SACAD: Scholarly Activities

Proteins evolve through sequence changes that shape structure, stability,

and function. Ancestral sequence reconstruction (ASR) infers ancestral

proteins from modern homologs, but many studies focus on sequence

inference without evaluating structural or energetic feasibility.

β-lactamases provide an ideal model due to their evolutionary diversity and

clinical relevance in antibiotic resistance.

Here, we present an integrated ASR workflow combining phylogenetic

inference (IQ-TREE), ancestral reconstruction, and structural and stability

validation using AlphaFold and FoldX. By reanalyzing a curated β-

lactamase dataset and comparing with a recent study (Risso et al., 2013),

we provide a controlled comparison of ancestral sequences, predicted

structures, and …

Extension Of The Local Vibrational Mode Theory To Periodic Systems, Filippo Bodo

Chemistry Theses and Dissertations

Over the years, vibrational spectroscopy was used to gain a deeper understanding of the electronic structure and the chemical bond in both molecular and periodic systems. In this framework, the Local Vibrational Mode Theory (LVMT), as first introduced by Konkoli and Cremer in 1998, provides a unique tool to quantify the strength of a chemical bond, and better interpret the molecular vibrational spectra, thanks to the adiabatic force constants ($k^a$) and the composition of normal modes (CNM). While LVMT was originally developed for molecular systems, its application to periodic solids has remained limited. This thesis presents a complete and systematic …

Microwave Synthesis And Characterization Of Fe2ptge Nanoparticles, Ally T. Fennell, David Carnevale

Chemistry Theses

Magnetic, semiconductor, and spintronic materials are vital to the functionality of devices from household appliances and sensors to medical and computing systems. This study discusses a novel synthesis and characterization of nanoscale Fe₂PtGe nanoparticles. The material was synthesized using microwave irradiation (175oC, 5 minutes) and characterized using XRD, XRF, TEM, and VSM. XRD of the synthesized particles correlates to a cubic crystal structured, indicating a face-centered cubic (fcc) platinum structure with iron and germanium incorporated in a disordered manner. XRF confirms the presence and relative ratios of iron, platinum, and germanium species. TEM imagery shows spherical nanoparticles with an average …

Computer-Aided Molecular Design To Identify More Environmentally Friendly Pfas, Melvin M. Keita

Williams Honors College, Honors Research Projects

The goal of this project is to inversely design alternatives to per- and polyfluoroalkyl substances (PFAS) using Computer-Aided Molecular Design (CAMD). PFAS, also described as “forever chemicals”, have been used in industry and consumer products since the 1940s. PFAS can be found in drinking water, food, food packaging, waste sites, and other sources. Exposure to different PFAS can lead to increased risks of some cancers, immune effects, and reproductive effects. Pulling from existing data, this project will use quantitative structure-property relationships (QSPRs) to design PFAS alternatives that possess optimal properties to prevent adsorption into drinking water and other potential sources …

Discovery Of The Multi-Ion Bridge Intermediate: A Computational Exploration Of The Mechanism For Azomethine Ylide Formation From N-Oxides, Martin J. Neal

Electronic Theses and Dissertations

Density functional theory (DFT) provides a method for calculating the ground-state energies of complex molecular systems through evaluating the electron density instead of the full wave function. When results match either experimental outcomes, calculations with DFT offer a computationally efficient method to help explain chemical phenomena. The transformation of tertiary amine N-oxides to azomethine ylides, a simple route to the precursor for 1,3-dipolar cycloadditions that result in the pyrrolidine scaffolds found in natural products, has received only minimal attention due to concerns that its mechanism includes a highly electrophilic intermediate. Utilizing DFT to model the mechanism of the conversion …

Quantum Chemical Methods And Multiscale Modeling In Computer-Aided Drug Design, Hunter W. La Force

Chemistry Theses and Dissertations

Computer-Aided Drug Design (CADD) leverages a diverse toolkit of computational methods to accelerate the discovery and development of novel therapeutics. Among these, quantum chemical calculations provide unparalleled accuracy in understanding molecular interactions, albeit at a higher computational cost. This accuracy is crucial for identifying and quantifying fundamental interactions that dictate drug efficacy and selectivity, as exemplified by our investigation of ruthenium polypyridyl complexes. These metal-based compounds are model systems for studying covalent coordination bonds between ruthenium and its ligands and noncovalent interactions with DNA and protein targets. Local Mode Vibrational Theory emerges as a powerful lens within this framework, enabling …

Modeling Molten Lithium Carbonate As Pollutant Absorbing Agent, Lucian G. Forestieri

Student Summer Scholars Manuscripts

Coal burning generates gaseous pollutants that are toxic to local environments and human health, namely hydrochloric acid and sulfur dioxide ( HCl and SO₂). Current methods for capturing these pollutants are flue gas desulfurization, which utilize solid or water- dissolved carbonates. This method, however, is inefficient mainly due to the product salts blocking further reactions. Molten carbonates may be a more efficient alternative. Experimental work cannot observe these reaction mechanisms, and the small number of current computational models do not match experimental properties. This work aims to develop a computational model of gaseous HCl scattering off the surface …

The Chemistry Of Heavy Elements: Probing Relativistic Chemical Bonding, Barbara Maria Teixeira Costa Peluzo

Chemistry Theses and Dissertations

The bottommost part of the periodic table has a unique chemistry, where the high velocities of the inner-shell electrons prevent their description by the usual Schrödinger equation. The resulting so-called relativistic effects have numerous chemical implications, on both macro and microscale, ranging from physical properties to reactivity. However, experimental probes on these intriguing atoms are limited by their natural availability and, more importantly, the danger associated with their radioactivity. Quantum chemical calculations, on the other hand, face the challenge of far more complex algebra, which demands substantial computational resources. Relativistic Hamiltonians, which act over all electrons in the system, are …

Advancing Coupled Cluster Methods: Tensor Factorization And Analytic Gradient Implementation, Tingting Zhao

Chemistry Theses and Dissertations

With the rapid advancement of computing capabilities, computational chemistry has become increasingly indispensable in both experiment design and the interpretation of experimental outcomes. Wave-function-based quantum mechanistic methods are highly sought after for their ability to provide high-accuracy data and their potential for systematic improvement. However, to extend their applicability to larger molecules, it is essential to employ rank-reducing approximations to these methods. This dissertation dedicates Chapters Three and Four to the development of rank-reduced methodologies. Additionally, beyond single-point energies, molecular geometries and properties of molecule-excited states hold paramount importance across diverse fields of chemistry. Hence, Chapter Five presents the work …

Contributions Of Tunneling In 8Π-6Π Electrocyclic Cascade Reactions Of Bicyclo[4.2.0]Octa-2,4-Diene Moieties, Ishika Jain, Claire Castro, William L. Karney

Featured Student Work

Six-electron electrocyclic reactions usually require relatively high temperatures; however recent research has shown that such reactions can occur at significantly lower temperatures in biosynthetic and biomimetic pathways. Pathways resulting in bicyclo[4.2.0]octa-2,4-diene moieties arise from thermally allowed 8π-6π electrocyclization cascade reactions of 1,3,5,7-octatetraenes, as in the biosynthesis of endiandric acids, elysiapyrones, and numerous other natural products. We report multidimensional tunneling calculations to explore the possible contribution of heavy-atom tunneling (e.g. by carbon) to biosynthetic pathways and biomimetic syntheses, and thus to provide a more complete picture of biochemical kinetics. M06-2X/cc-pVDZ calculations on the 8π-6π cascade cyclizations of methylated octatetraene model systems …

The Investigation Of Singlet Fission From The Perspective Of Hierarchy Of Pure States (Hops), Tao (James) Chen

Chemistry Theses and Dissertations

This thesis provides a preliminary investigation of singlet fission from the perspective of Hierarchy of pure states (HOPS), which provides a numerical exact solution for the investigation of a series of open quantum systems. Since the inception of the concept of singlet fission about half a century ago, this photo-physical process has attracted the attention of a multitude of researchers and has been extensively studied theoretically and experimentally. However, these previous methods for the investigation of singlet fission focus more or less on tackling the underlying mechanisms of singlet fission from the perspective of perturbation. So far, the HOPS method …

The Investigation Of Singlet Fission From The Perspective Of Hierarchy Of Pure States (Hops), Tao (James) Chen

Chemistry Theses and Dissertations

This thesis provides a preliminary investigation of singlet fission from the perspective of Hierarchy of pure states (HOPS), which provides a numerical exact solution for the investigation of a series of open quantum systems. Since the inception of the concept of singlet fission about half a century ago, this photo-physical process has attracted the attention of a multitude of researchers and has been extensively studied theoretically and experimentally. However, these previous methods for the investigation of singlet fission focus more or less on tackling the underlying mechanisms of singlet fission from the perspective of perturbation. So far, the HOPS method …

The Decomposition Of Normal Vibrational Modes In Different Chemistry Problems, Mateus Macedo Quintano

Chemistry Theses and Dissertations

The least action principle yields the Euler-Lagrange equations, which explain molecular vibrations in minimizing action. Subsequently, the Lagrangian gives rise to the equations of motion using the Euler-Lagrange equations. We can then solve the characteristic value problem to obtain normal vibrational modes. Ultimately, the vibrational spectrum of a molecule can be extracted from the characteristic values. Normal coordinates are linear combinations of internal or Cartesian coordinates. However, the delocalization of normal vibrational modes across the molecule restricts the direct use of normal mode frequencies and force constants for measuring bond strength. From the force constant matrix and the normal mode …

New Methods For Core-Hole Spectroscopy Based On Coupled Cluster Theory, Megan Simons

Chemistry Theses and Dissertations

X-ray absorption spectra (XAS) is a method used to investigate atomic local structure and electronic states. Coupled cluster method is a numerical method used for describing many-body systems and electron correlation in a wavefunction. When equation-of-motion coupled cluster is used in XAS calculations, the ground state is applied to the excitation operator, which excites or ionizes the electron. This causes a large orbital relaxation error, normally ~5 eV, which leads to the need for triple excitations in order to obtain accurate results.

This dissertation introduces a coupled cluster method that uses "transition potential" reference orbitals to reduce the orbital relaxation …

Modeling Excited State Processes In Molecular Aggregates By Constructing An Adaptive Basis For The Hierarchy Of Pure States, Leonel Varvelo

Chemistry Theses and Dissertations

Simulating excitation energy transfer (EET) in molecular materials is of crucial importance for the development of and understanding of materials such as organic photovoltaics and photosynthetic systems and further development of novel materials. The Hierarchy of Pure States (HOPS) is an exact framework for the time evolution of an open quantum system in which a hierarchy of stochastic wave functions are propagated in time. The adaptive HOPS (adHOPS) method achieves size-invariant scaling with the number of simulated molecules for sufficiently large aggregates by using an adaptive basis that moves with the excitation through the material. To demonstrate the power of …

Exploring Protein Conformations And Functions Through Molecular Dynamics Simulations And Machine Learning, Hao Tian

Chemistry Theses and Dissertations

Proteins are essential biomacromolecules that perform a variety of critical functions in living organisms. The tertiary structure of a protein plays a crucial role in its biological activity as it determines how the protein interacts with other molecules. Consequently, understanding protein conformation and function is an important area of research with implications in medicine, biotechnology, and other fields.

The first part of this dissertation focuses on protein allostery, a process by which proteins transmit perturbations caused by binding at one site to a distal site, thereby regulating activity. With the development of computational methods like molecular dynamics simulations and machine …

Advanced Insights Regarding Both Micro- And Macro-Molecules In Various Environments: Showcasing The Local Mode Theory As A Powerful Tool., Alexis A. A. Delgado

Chemistry Theses and Dissertations

A majority of the research featured in my dissertation has involved the derivation of direct quantitative measures of intrinsic strength from quantum chemical calculations of molecular systems. In my works I applied Local Vibrational Mode Theory (LVMT) to 1) transform normal modes to local modes, via the elimination of all mode-mode coupling, to obtain local mode force constants (i.e. direct measures of intrinsic strength), 2) in combination with the Unified Reaction Valley Approach, unravel detailed information about bond breaking/formation processes that occur along a reaction, and 3) decompose individual normal modes into percentages of local mode contributions. This dissertation encompasses …

Computational Investigations Into Astrochemical Inorganic Oxides, Ammonia Borane, And Genetic Algorithms, E. Michael Valencia

Honors Theses

The formulations of quantum mechanics in the early 1900s were exciting theoretical discoveries, but were not practical to apply until the advent of computers and the subsequent computational methods in 1951. With the introduction of tractable simplifications, procedures such as Hartree-Fock allowed for determination of properties of non-trivial systems. Presently, huge leads of computational power have allowed for extremely precise, quantitative work that can be applied to the human body, synthesis, or even astrochemical processes. This thesis presents works concerning 1) the history of quantum mechanics; 2) a brief primer on computational chemistry and its methods; 3) inorganic oxides in …

Unraveling Molecular Mechanisms Of Antibiotic Resistance Through Multiscale Simulations And Explainable Machine Learning, Zilin Song

Chemistry Theses and Dissertations

Pathogen resistance to β-lactam antibiotics compromises effective treatments of superbug infections. One major source of β-lactam resistance is the bacterial production of β-lactamases, which could effectively hydrolyze β-lactam drugs. In this thesis, the hydrolysis of various β-lactam antibiotics by class A serine-based β-lactamases (ASβLs) were investigated using hybrid Quantum Mechanical / Molecular Mechanical (QM/MM) minimum energy pathway (MEP) calculations and explainable machine learning (ML) approaches. The TEM-1/benzylpenicillin acylation reaction with QM/MM chain-of-states reaction pathways was firstly revisited. I proposed two decomposition methods for energy contribution analysis based on perturbing ML regression models. Both methods were shown to be model implementation …

Computational Modeling As A Tool For Designing Ligands And Receptors, Waqas S. Awan

Legacy Theses & Dissertations (2009 - 2024)

Computational methods can be used for a wide range of applications, especially regarding DNA and RNA. Interactions such as sugar torsions, receptor-ligand interactions, ligand docking/drug docking, receptor modeling, and drug design are excellent candidates for computational analysis and in silico experiments. The use of molecular dynamics software (GROMACS) coupled with molecular design software (MOE) produce insights that may have been otherwise difficult to assess. All these problems are academic in nature but have practical uses outside of academia. Understanding alternate linkages can lead to antibiotic assays to address potential superbug epidemics. Modeling DNA superstructures can provide insight into how large …