Chemistry Commons^™

Sars-Cov-2 Main Protease Targeting Potent Fluorescent Inhibitors: Repurposing Thioxanthones, Gönül Saadet Batibay, Eyüp Meti̇n

Turkish Journal of Chemistry

The coronavirus disease, COVID-19, is the major focus of the whole world due to insufficient treatment options. It has spread all around the world and is responsible for the death of numerous human beings. The future consequences for the disease survivors are still unknown. Hence, all contributions to understand the disease and effectively inhibit the effects of the disease have great importance. In this study, different thioxanthone based molecules, which are known to be fluorescent compounds, were selectively chosen to study if they can inhibit the main protease of SARS-CoV-2 using various computational tools. All candidate ligands were optimized, molecular …

The Future Of Alternative Energy? Simulating Methyl Stearate Pyrolysis Via Molecular Dynamic Processes, Sarah J. Adeoye

Graduate Theses/Dissertations

The process of extracting and refining crude oil is both expensive and environmentally hazardous. The synthesis of biodiesel sourced from vegetable oils is a renewable process and less hazardous to the environment. Therefore, we seek to understand the pyrolysis procedure at an atomic level in hopes of optimizing future fuel viability. Herein, I analyze methyl stearate (a component of biodiesel) using an in-house database of ab initio trajectories, each simulating 1.0 ps (with 1.0 fs resolution). These jobs were observed for significant bond-breaking/forming events, the type of fragments produced, and the exact position and time for each event. Statistical analysis …

Molecular Biofilm Inhibitors On Noble Metal Surfaces, Mahamadu Tiah Mahama

Dissertations and Theses

Biofilms are the state microorganisms on surfaces which negatively impact many of processes taking place on them. For example, most microbial infections are attributed to biofilm forma- tion, with bacteria in biofilms exhibiting an antibiotic resistance several orders of magnitude than planktonic bacteria. Therefore, developing antibiofilm agents and understanding their mechanism of inhibition is essential. Citrate functionalized gold nanoparticles are well known for their an- tibiofilm properties. Recently, hybrid bisphosphonate polyoxovanadate gold nanoparticles showed a great potential to inhibit both gram-negative and gram-positive bacteria biofilm formation. How- ever, it is unknown how this species interacts with the metal surface, its …

Turning Density Functional Theory Calculations Into Molecular Mechanics Simulations : Establishing The Fluctuating Density Model For Rna Nucleobases, Christopher A. Myers

Legacy Theses & Dissertations (2009 - 2024)

Molecular mechanics (MD) simulations and density functional theory (DFT) have been the backbone of computational chemistry for decades. Due to its accuracy and computational feasibility, DFT has become the go-to method for theoretically predicting interaction energies, polarizability, and other electronic properties of small molecules at the quantum mechanical level. Although less fundamental than DFT, molecular mechanics (MM) algorithms have been just as influential in the fields of biology and chemistry, owing their success to the ability to compute measurable, macroscopic quantities for systems with tens of thousands to hundreds of thousands of atoms at a time. Nevertheless, MD simulations would …

Molecular Dynamics Simulations Of The Adenylate Kinase Enzyme And Its Mutant States, Beata Izabella Dulko Smith

Chemistry & Biochemistry Dissertations - Archive

Adenylate kinase (AK) is a small, monomeric enzyme present across all domains of life. It is responsible for maintaining homeostasis of an intracellular adenylate pool and catalyzes a reversible transfer of the phosphoryl group from NTP (nucleoside triphosphate) to NMP producing two NDP molecules. While most known isoforms take ATP as phosphate donor, AK3 present in mitochondrial matrix employs GTP. Crystallographic investigations revealed that the basis for its selectivity for GTP over ATP came from an additional hydrogen bond between guanosine’s O6 and backbone nitrogen of threonine is responsible for recognition of GTP. Molecular dynamics (MD) simulations have demonstrated that …

Probing Mechanisms Of Binding And Allostery In The Sars-Cov-2 Spike Omicron Variant Complexes With The Host Receptor: Revealing Functional Roles Of The Binding Hotspots In Mediating Epistatic Effects And Communication With Allosteric Pockets, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we performed all-atom MD simulations of RBD–ACE2 complexes for BA.1, BA.1.1, BA.2, and BA.3 Omicron subvariants, conducted a systematic mutational scanning of the RBD–ACE2 binding interfaces and analysis of electrostatic effects. The binding free energy computations of the Omicron RBD–ACE2 complexes and comprehensive examination of the electrostatic interactions quantify the driving forces of binding and provide new insights into energetic mechanisms underlying evolutionary differences between Omicron variants. A systematic mutational scanning of the RBD residues determines the protein stability centers and binding energy hotpots in the Omicron RBD–ACE2 complexes. By employing the ensemble-based global network analysis, we …

Ligand-Based Virtual Screening And Molecular Docking Of Benzimidazoles As Potential Inhibitors Of Triosephosphate Isomerase Identified New Trypanocidal Agents, Lenci K. Vazquez-Jimenez, Alfredo Juarez-Saldivar, Rogelio Gomez-Escobedo, Timoteo Delgado-Maldonado, Domingo Mendez-Alvarez, Isidro Palos, Debasish Bandyopadhyay, Carlos Gaona-Lopez, Eyra Ortiz-Perez, Benjamin Nogueda-Torres, Esther Ramirez-Moreno, Gildardo Rivera

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Trypanosoma cruzi (T. cruzi) is a parasite that affects humans and other mammals. T. cruzi depends on glycolysis as a source of adenosine triphosphate (ATP) supply, and triosephosphate isomerase (TIM) plays a key role in this metabolic pathway. This enzyme is an attractive target for the design of new trypanocidal drugs. In this study, a ligand-based virtual screening (LBVS) from the ZINC15 database using benzimidazole as a scaffold was accomplished. Later, a molecular docking on the interface of T. cruzi TIM (TcTIM) was performed and the compounds were grouped by interaction profiles. Subsequently, a selection of compounds was made based …

Implications Of Metal Coordination In Damage And Recognition Of Nucleic Acids And Lipid Bilayers, Ana Dreab

Chemistry & Biochemistry Theses & Dissertations

Metal ions have a myriad of biological functions from structural stability to enzymatic (de)activation and metabolic electron transfer. Redox-active metals also mediate the formation of reactive oxygen species which may either cause oxidative damage or protect cellular components. Computational modeling is used here to investigate the role of (1) metal-ion binding to antimicrobial peptides, (2) metal-ion removal and disulfide formation on zinc finger (ZF) proteins, and (3) coordination of thiones/selones for the prevention of metal-mediated redox damage.

Piscidins, natural-occurring antimicrobial peptides, efficiently kill bacteria by targeting their membranes. Their efficacy is enhanced in vitro by metal-binding and the presence of …

Computer Simulations And Network-Based Profiling Of Binding And Allosteric Interactions Of Sars-Cov-2 Spike Variant Complexes And The Host Receptor: Dissecting The Mechanistic Effects Of The Delta And Omicron Mutations, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we combine all-atom MD simulations and comprehensive mutational scanning of S-RBD complexes with the angiotensin-converting enzyme 2 (ACE2) host receptor in the native form as well as the S-RBD Delta and Omicron variants to (a) examine the differences in the dynamic signatures of the S-RBD complexes and (b) identify the critical binding hotspots and sensitivity of the mutational positions. We also examined the differences in allosteric interactions and communications in the S-RBD complexes for the Delta and Omicron variants. Through the perturbation-based scanning of the allosteric propensities of the SARS-CoV-2 S-RBD residues and dynamics-based network centrality and …

Repurposing Lansoprazole And Posaconazole To Treat Leishmaniasis: Integration Of In Vitro Testing, Pharmacological Corroboration, And Mechanisms Of Action, Yash Gupta, Steven Goicoechea, Jesus G. Romero, Raman Mathur, Thomas R. Caulfield, Daniel P. Becker, Ravi Durvasula, Prakasha Kempaiah

Chemistry: Faculty Publications and Other Works

Leishmaniasis remains a serious public health problem in many tropical regions of the world. Among neglected tropical diseases, the mortality rate of leishmaniasis is second only to malaria. All currently approved therapeutics have toxic side effects and face rapidly increasing resistance. To identify existing drugs with antileishmanial activity and predict the mechanism of action, we designed a drug-discovery pipeline utilizing both in-silico and in-vitro methods. First, we screened compounds from the Selleckchem Bio-Active Compound Library containing ~1622 FDA-approved drugs and narrowed these down to 96 candidates based on data mining for possible anti-parasitic properties. Next, we completed preliminary in-vitro testing …

Structural And Computational Studies Of The Sars-Cov-2 Spike Protein Binding Mechanisms With Nanobodies: From Structure And Dynamics To Avidity-Driven Nanobody Engineering, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Nanobodies provide important advantages over traditional antibodies, including their smaller size and robust biochemical properties such as high thermal stability, high solubility, and the ability to be bioengineered into novel multivalent, multi-specific, and high-affinity molecules, making them a class of emerging powerful therapies against SARS-CoV-2. Recent research efforts on the design, protein engineering, and structure-functional characterization of nanobodies and their binding with SARS-CoV-2 S proteins reflected a growing realization that nanobody combinations can exploit distinct binding epitopes and leverage the intrinsic plasticity of the conformational landscape for the SARS-CoV-2 S protein to produce efficient neutralizing and mutation resistant characteristics. Structural …

Allosteric Determinants Of The Sars-Cov-2 Spike Protein Binding With Nanobodies: Examining Mechanisms Of Mutational Escape And Sensitivity Of The Omicron Variant, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against the SARS-CoV-2 virus and resilience against mutational escape. In this study, we performed a comprehensive computational analysis of the SARS-CoV-2 spike trimer complexes with single nanobodies Nb6, VHH E, and complex with VHH E/VHH V nanobody combination. We combined coarse-grained and all-atom molecular simulations and collective dynamics analysis with binding free energy scanning, perturbation-response scanning, and network centrality analysis to examine mechanisms of nanobody-induced allosteric modulation and cooperativity in the SARS-CoV-2 spike trimer complexes with these nanobodies. By quantifying energetic and allosteric …

Ultrafast Dynamics Of Nitro−Nitrite Rearrangement And Dissociation In Nitromethane Cation, Mi'kayla D. Word, Hugo Andres Lopez Pena, Derrick Ampadu Boateng, Shane L. Mcpherson, Gennady L. Gutsev, Lavrenty Gutsev, Ka Un Lao, Katharine M. Tibbetts

Chemistry Publications

We report new insights into the ultrafast rearrange- ment and dissociation dynamics of nitromethane cation (NM+) using pump−probe measurements, electronic structure calculations, and ab initio molecular dynamics simulations. The “roaming” nitro−nitrite rearrangement (NNR) pathway involving large- amplitude atomic motion, which has been previously described for neutral nitromethane, is demonstrated for NM+. Excess energy resulting from initial population of the electronically excited D2 state of NM+ upon strong-field ionization provides the necessary energy to initiate NNR and subsequent dissociation into NO+. Both pump−probe measurements and molecular dynamics simulations are consistent with the completion of NNR within 500 fs of ionization with …

Virtual Screening, Drug-Likeness Analysis, And Molecular Docking Study Of Potentialsevere Acute Respiratory Syndrome Coronavirus 2 Main Protease Inhibitors, Nikola Nedeljkovic, Milos Nikolic, Ana Stankovic, Nevena Jeremic, Dusan Tomovic, Andriana Bukonjic, Gordana Radic, Marina Mijajlovic

Turkish Journal of Chemistry

Due to the length of time required to develop specific antiviral agents, the World Health Organization adopted the strategy of repurposing existing medications to treat Coronavirus disease 2019 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease is possible biological target for potential antiviral drugs. We selected various compounds from PubChem database based on the structure of main protease inhibitors in Protein Data Bank database. Ten compounds showed nontumorigenic and nonmutagenic potential and met Egan's and Lipinski's rules. Molecular docking analysis was performed using AutoDock Vina software. Based on number and type of key binding interactions, as well as …

Nonhematopoietic Erythropoietin: A Study Of Signaling, Structure, And Behavior, Nicholas John Pekas

Dissertations and Theses

Erythropoietin (EPO) is a cytokine hormone known for initiating red blood cell proliferation by binding to its homodimer receptor (EPOR)2 in the bone marrow. Recent progress in neurobiology has shown that EPO also exerts robust neurotrophic and neuroprotective activity in the CNS. It is widely thought that EPO’s neurotrophic activity is centrally involved in its antidepressant and cognitive enhancing effects. However, EPO’s potent erythropoietic effects prevent it from being used in the clinic to treat psychiatric disorders. A chemically engineered non-erythropoietic derivative of EPO, carbamoylated EPO (CEPO), produces psychoactive effects without activating hematopoiesis. However, CEPO is expensive to produce and …

Characterizing The Effects Of Solvent And Analyte Properties On Ionization Efficiency By Novel Field-Free And Field-Enabled Ionization Techniques, Kinkini Udara Jayasundara

Graduate Theses, Dissertations, and Problem Reports (ETD)

In recent years the mass spectrometry (MS) area of field and/or direct analysis has grown dramatically. As a result, field-portable and miniaturized mass spectrometers, introduced only a few years ago, are proliferating. A highly desired feature for field-portable MS, or in-field analysis, is the ability to use ionization techniques requiring very little sample preparation as well as an ability to generate the ions under ambient conditions. Recently, a new ambient ionization technique termed vibrating sharp-edge spray ionization (VSSI) has been introduced which overcomes the field-portable limitations of other spray-based methods including the requirements for auxiliary components (e.g., nebulizing gas and …

Multilevel Computational Investigation Into The Dynamics And Reaction Mechanisms Of Non-Heme Iron And 2-Oxoglutarate Dependent Enzymes, Shobhit Sanjeev Chaturvedi

Dissertations, Master's Theses and Master's Reports

Computational chemistry methods have been extensively applied to investigate biological systems. This dissertation utilizes a multilevel computational approach to explore the dynamics and reaction mechanisms of two groups of enzymes belonging to non-heme Fe(II) and 2-oxoglutarate (2OG) dependent superfamily – histone lysine demethylases from class 7 and ethylene forming enzyme (EFE). Chapter 2 uncovers the role of conformational dynamics in the substrate selectivity of histone lysine demethylases 7A and 7B. The molecular dynamics (MD) simulations of the two enzymes revealed the importance of linker flexibility and dynamics in relative orientations of the reader (PHD) and the catalytic (JmjC) domains. Chapter …

Self-Assembly Of Black Cumin Oil-Based Nanoemulsion On Various Surfactants: A Molecular Dynamics Study, Aulia Fikri Hidayat, Taufik Muhammad Fakih

Makara Journal of Science

Black cumin is commonly used as traditional medicine due to its wide range of pharmacological potential. Black cumin oil (BCO) was often prepared as nanoemulsion to improve its solubility, stability, and bioavailability. This study was conducted to investigate the molecular behavior as well as structural evolution of BCO-surfactant systems during self-assembly micellization using molecular dynamics (MD) simulations. Several BCO constituents and variations of surfactants were employed to model BCO-surfactant systems. 50 ns of MD simulations were performed to elucidate their evolution of structures and physicochemical properties during formation. Results showed that BCO-tween20 and BCO-lecithin were able to form spherical-shaped micelles …

Molecular Mechanisms Underlying Enhanced Hemichannel Function Of A Cataract-Associated Cx50 Mutant, Jun-Jie Tong, Umair Khan, Bassam George Haddad, Peter J. Minogue, Eric C. Beyer, Vivian M. Berthoud, Steve L. Reichow, Lisa Ebihra

Chemistry Faculty Publications and Presentations

Connexin-50 (Cx50) is among the most frequently mutated genes associated with congenital cataracts. Although most of these disease-linked variants cause loss of function because of misfolding or aberrant trafficking, others directly alter channel properties. The mechanistic bases for such functional defects are mostly unknown. We investigated the functional and structural properties of a cataract-linked mutant, Cx50T39R (T39R), in the Xenopus oocyte system. T39R exhibited greatly enhanced hemichannel currents with altered voltage-gating properties compared to Cx50 and induced cell death. Coexpression of mutant T39R with wild-type Cx50 (to mimic the heterozygous state) resulted in hemichannel currents whose properties were indistinguishable from …

Modeling Vitexin And Isovitexin Flavones As Corrosion Inhibitors For Aluminium Metal, Abdullahi Muhammad Ayuba, Umaru Umar

Karbala International Journal of Modern Science

Theoretically, the aluminium corrosion inhibitive performance of vitexin (VTX) and isovitexin (SVT) were evaluated with a view of establishing the mechanism of the inhibition process. Calculations which include the consideration of several global descriptors were studied to describe and correlate the reactivity of the molecules with the computed descriptors. First and second-order condensed Fukui functions were employed to analyze local reactivity parameters, while simulations involving the adsorbed molecules on Al (1 1 0) surface were conducted through quench dynamic simulations and the mechanism of physical adsorption was established with SVT relatively been a better inhibitor on Al surface than VTX.

Tuning Protein Dynamics To Sense Rapid Endoplasmic-Reticulum Calcium Dynamics, Xiaonan Deng, Xin-Qiu Joe Yao, Ken Berglund, Bin Dong, Daniel Ouedraogo, Mohammad A. Ghane, You Zhuo, Cheyenne Mcbean, Zheng Zachory Wei, Samer Gozem, Shan P. Yu, Ling Wei, Ning Fang, Angela M. Mabb, Giovanni Gadda, Donald Hamelberg, Jenny J. Yang

Chemistry Faculty Publications

Multi-scale calcium (Ca2+) dynamics, exhibiting wide-ranging temporal kinetics, constitutes a ubiquitous mode of signal transduction. We report a novel endoplasmic-reticulum (ER)-targeted Ca2+ indicator, R-CatchER, which showed superior kinetics in vitro (koff≥2×103 s−1, kon≥7×106 M−1 s−1) and in multiple cell types. R-CatchER captured spatiotemporal ER Ca2+ dynamics in neurons and hotspots at dendritic branchpoints, enabled the first report of ER Ca2+ oscillations mediated by calcium sensing receptors (CaSRs), and revealed ER Ca2+-based functional cooperativity of CaSR. We elucidate the mechanism of R-CatchER and propose a principle to rationally design genetically encoded Ca2+ indicators with a single Ca2+-binding site …

Computational Investigation Of Nanoparticle Immersion And Selfassembly, Tara Allison Tyler Nitka

Open Access Theses & Dissertations

Both neutral and charged nanoparticles with a variety of compositions, shapes, and sizes have beenpreviously prepared. These nanoparticles have been demonstrated to self-assemble into a variety of superlattices and binary superlattices both in bulk solution and at surfaces of solutions, and the structures formed by self-assembly have been shown to depend on nanoparticle chemistry and charge as well as on whether assembly takes place at a surface or in bulk. Furthermore, the prepared isolated and self-assembled nanoparticles have a number of biomedical, nanotechnology, and industrial applications. In this Dissertation, I present my research on three general topics. First, I will …

Bridging The 12-6-4 Model And The Fluctuating Charge Model, Pengfei Li

Chemistry: Faculty Publications and Other Works

Metal ions play important roles in various biological systems. Molecular dynamics (MD) using classical force field has become a popular research tool to study biological systems at the atomic level. However, meaningful MD simulations require reliable models and parameters. Previously we showed that the 12-6 Lennard-Jones nonbonded model for ions could not reproduce the experimental hydration free energy (HFE) and ion-oxygen distance (IOD) values simultaneously when ion has a charge of +2 or higher. We discussed that this deficiency arises from the overlook of the ion-induced dipole interaction in the 12-6 model, and this term is proportional to 1/r …

Computational Analysis Of Type 3 Iodothyronine Deiodinase: Potential Inhibitors, Substrate Binding, And Dimer Structure, Eric Scott Marsan

Chemistry & Biochemistry Theses & Dissertations

Thyroid hormones (THs) in mammalian tissues are crucial for development and maintaining metabolic homeostasis. Iodothyronine deiodinases (Dios) remove iodines from THs by a selenocysteine (Sec) residue, which either activates or inactivates them. Halogen bonding (XB) has been proposed to describe the interaction between the Se and I atoms of the T4-Dio complex. Disruption of TH homeostasis by xenobiotics, such as polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) can cause deleterious effects on the endocrine system. Experimental studies have indicated that PBDEs and PCBs could disrupt TH homeostasis by inhibiting Dio through XB formation. However, no current quantitative study exists …

The Effect Of The Apolipoprotein A1 (Apoa1): The Stability And Folding In Potassium Chloride Environment, Alexandra Paladian

Honors Theses

Healthy levels of potassium chloride (KCl) can significantly affect the workings of the cholesterol level of the human body and how they pertain to an individual person. The search for a better salt additive for the human diet can provide a better option for people who experience high cholesterol levels and heart disease. The study focuses on the experimental design of the Molecular Dynamic (MD) simulation of the Apolipoprotein A1 (APOA1) in the potassium ion solution environment to determine the stability and folding of the protein. The study also compares its data to the previous experimental design of chloride ions …

Molecular Dynamic Simulation Of The Complex Folding Patterns Of Apolipoprotein A1 In Various Concentrations Of Potassium Chloride, Hannah Holmberg

Honors Theses

Apopliprotein or ApoA-1 is a complex lipoprotein that functions in the removal of cholesterol from the blood, removing cholesterol from the area around white blood cells and promoting the excretion of lipids through the lymphatic system. Previous research has found that ApoA-1 shows both folded and unfolded conformations depending on the concentration of NaCl in solution in the water around it. The protein was studied using molecular dynamics simulations. Once this state of equilibrium was reached, various structural properties of the protein were measured including the radius of gyration and the radial distribution function. The goal of the project was …

Computational And Experimental Investigation Into The Determinants Of Protein Structure, Folding, And Stability In The Β-Grasp Superfamily, John T. Bedford Ii

Chemistry & Biochemistry Theses & Dissertations

Elucidating the mechanisms of protein folding and unfolding is one of the greatest scientific challenges in basic science. The overarching goal is to predict three-dimensional structures from their amino acid sequences. Understanding the determinants of protein folding and stability can be facilitated through the study of evolutionarily related but diverse proteins. Insights can also be gained through the study of proteins from extremophiles that may more closely resemble the primordial proteins. In this doctoral research, three aims were accomplished to characterize the structure, folding and unfolding behavior within the β-grasp superfamily. We propose that the determinants of structure, stability, and …

Subsets Of Adjacent Nodes (Soan): A Fast Method For Computing Suboptimal Paths In Protein Dynamic Networks, Thomas Dodd, Xin-Qiu Joe Yao, Donald Hamelberg, Ivaylo Lvanov

Chemistry Faculty Publications

Suboptimal path analysis in a protein structural or dynamical network becomes increasingly popular for identifying critical residues involved in allosteric communication and regulation. Several software packages have been developed for calculating suboptimal paths, including NetworkView, WISP, and CNAPATH (Bio3D). Although these packages work well for biological systems of moderate sizes, they either dramatically slow down or are subjected to accuracy issues when applied to large systems such as supramolecular complexes. In this work, we develop a new method called SOAN, which implements a modified version of Yen’s algorithm for finding loopless k-shortest paths. Instead of searching the entire protein …

Using Molecular Dynamics Simulations To Understand Receptor-Complex Communication And Signaling, Hannah Margaret Hoag

Theses and Dissertations

The overarching purpose of this document is to use Computer-aided drug design and Molecular dynamic simulations to better understand elusive drug-receptor interactions, as well as various types of inter-receptor signaling. Chapter One introduces the theory and importance of Computer-aided drug design and the methodology used in both Chapters Two and Three.

Chapter Two uncovers the relationship between the well-studied ABCB1 transporter and a newly identified drug known as Xanthohumol (XN). XN is compared to a commonly used drug, Doxorubicin (DOX), in this chapter. If the ABCB1 transporter can be properly inhibited, cancer-fighting drugs will be able to stay within the …

Structural Rearrangement Of Neisseria Meningitidis Transferrin Binding Protein A (Tbpa) Prior To Human Transferrin Protein (Htf) Binding, Gi̇zem Nur Duran, Mehmet Özbi̇l

Turkish Journal of Chemistry

Gram-negative bacterium Neisseria meningitidis, responsible for human infectious disease meningitis, acquires the iron (Fe3+) ion needed for its survival from human transferrin protein (hTf). For this transport, transferrin binding proteins TbpA and TbpB are facilitated by the bacterium. The transfer cannot occur without TbpA, while the absence of TbpB only slows down the transfer. Thus, understanding the TbpA-hTf binding at the atomic level is crucial for the fight against bacterial meningitis infections. In this study, atomistic level of mechanism for TbpA-hTf binding is elucidated through 100 ns long all-atom classical MD simulations on free (uncomplexed) TbpA. TbpA protein underwent conformational …