Digital Commons Network^™

Dissection Of The Factors Affecting Formation Of A Ch∙∙∙O H-Bond. A Case Study, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

Quantum calculations are used to examine how various constituent components of a large molecule contribute to the formation of an internal CH∙∙∙O H-bond. Such a bond is present in the interaction between two amide units, connected together by a series of functional groups. Each group is removed one at a time, so as to monitor the effect of each upon the H-bond, and thereby learn the bare essentials that are necessary for its formation, as well as how its presence affects the overall molecular structure. Also studied is the perturbation caused by change in the length of the aliphatic chain …

Synthesis And Structure−Activity Relationships Of Tambjamines And B‑Ring Functionalized Prodiginines As Potent Antimalarials, Papireddy Kancharla, Jane Xu Kelly, Kevin A. Reynolds

Chemistry Faculty Publications and Presentations

Synthesis and antimalarial activity of 94 novel bipyrrole tambjamines (TAs) and a library of B-ring functionalized tripyrrole prodiginines (PGs) against a panel of Plasmodium falciparum strains are described. The activity and structure–activity relationships demonstrate that the ring-C of PGs can be replaced by an alkylamine, providing for TAs with retained/enhanced potency. Furthermore, ring-B of PGs/TAs can be substituted with short alkyl substitutions at either 4-position (replacement of OMe) or 3- and 4-positions without impacting potency. Eight representative TAs and two PGs have been evaluated for antimalarial activity against multidrug-resistant P. yoelii in mice in the dose range of 5–100 mg/kg …

Identification Of Inhibitors That Target Dual-Specificity Phosphatase 5 Provide New Insights Into The Binding Requirements For The Two Phosphate Pockets, Terrence S. Neumann, Elise A. Span, Kelsey S. Kalous, Robert D. Bongard, Adam Gastonguay, Michael A. Lepley, Raman G. Kutty, Jaladhi Nayak, Chris Bohl, Rachel G. Lange, Majher I. Sarker, Marat R. Talipov, Rajendra Rathore, Ramani Ramchandran, Daniel S. Sem

Chemistry Faculty Research and Publications

Background: Dual-specificity phosphatase-5 (DUSP5) plays a central role in vascular development and disease. We present a p-nitrophenol phosphate (pNPP) based enzymatic assay to screen for inhibitors of the phosphatase domain of DUSP5.

Methods: pNPP is a mimic of the phosphorylated tyrosine on the ERK2 substrate (pERK2) and binds the DUSP5 phosphatase domain with a Km of 7.6 ± 0.4 mM. Docking followed by inhibitor verification using the pNPP assay identified a series of polysulfonated aromatic inhibitors that occupy the DUSP5 active site in the region that is likely occupied by the dual-phosphorylated ERK2 substrate tripeptide (pThr-Glu-pTyr). Secondary assays …

Fluorinated Metallo Phthalocyanines For Chemical And Biological Catalysis, Hemantbhai H. Patel

Seton Hall University Dissertations and Theses (ETDs)

The rational design of robust oxidation catalysts based on organic molecules is hindered by the presence of labile C-H bonds. We have shown recently that replacing all C-H bonds by a combination of fluoro- and perfluoro-groups in a bioinspired Cytochrome P450 model based on a phthalocyanine, Pc, scaffold results in a stable yet reactive oxidation catalyst. The Pc cobalt complex catalyzes, for example, the aerobic oxidation of thiols to disulfides, a reaction of both biological significance and industrial importance.

The presence of robust C-F bonds, however, renders the catalyst unsuitable for attachment to solid-state supports, except via van der Waals …

Screening Protein Ligand Interactions Using Microelectrode Arrays, Sakshi Uppal

Arts & Sciences Graduate Student Theses and Dissertations

G proteins comprising of α subunit and βγ dimer are signaling proteins that play essentialroles in various pathological conditions. Direct modulation of these G proteins (specifically Gα subunit) using small chemical probes to elucidate their acute function is of great value. YM-254890 is a small molecule which is the first selective inhibitor of a class of G proteins, Gαq. However, despite its biological importance, this molecule is not available to researchers. In addition, the complex core structure of this cyclic depsipeptide has thwarted efforts to obtain a series of analogs by total synthesis. Moeller lab sought to overcome this obstacle …

Manipulating Electron Transfer Reactions From Micro- To Preparative Scale, Matthew Duane Graaf

Arts & Sciences Graduate Student Theses and Dissertations

The utilization of electron transfer reactions has allowed the transformation of a variety of substrates from polymer surfaces to highly functionalized organic molecules. The intricacies of these electron transfer reactions have been utilized to develop a new platform for building and studying addressable molecular libraries as they interact with biological targets. As a low cost, reusable alternative to other methods of these studying binding interactions, microelectrode arrays are beginning to gain traction with the scientific community as we continually push the limits of their potential. Additionally, the electron transfer techniques used to build the molecular libraries can be expanded to …

Structural And Functional Analysis Of The Reaction Center Complexes From The Photosynthetic Green Sulfur Bacteria, Guannan He

Arts & Sciences Graduate Student Theses and Dissertations

The reaction center (RC) complex of the green sulfur bacterium Chlorobaculum tepidum is composed of the Fenna-Matthews-Olson (FMO) antenna protein and the reaction center core (RCC) complex. The RCC complex has four subunits: PscA, PscB, PscC, and PscD. The structure of the intact and functional FMO-RCC complex was studied by chemically cross-linking the purified sample followed by biochemical and spectroscopic analysis. The interaction sites of the cross-linked complex were also studied using LC-MS/MS. A structural model is proposed based on those results. In addition, the RCC complexes were purified, both the PscA-PscC complex from the Chlorobaculum tepidum and the PscA-PscB …

Structure And Function Of Cytochrome Containing Electron Transport Chain Proteins From Anoxygenic Photosynthetic Bacteria, Erica Lois-Wunderlich Majumder

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation examines the structure and function of photosynthetic proteins that contain c-type heme cofactors that function in the electron transport chains of anaerobic phototrophic bacteria. The diversity and range of these cytochromes proteins was explored. Then, individual proteins were studied in detail. The diheme cytochrome c from Heliobacteria modesticaldum was studied using hydrogen deuterium exchange mass spectrometry and homology modeling. A structural model of the protein and a mechanism for the cytochrome bc complex was proposed. Next, the monoheme cytochrome c subunit from the Alternative Complex III from the Filamentous Anoxygenic Phototrophs was studied using biochemistry and found to …

Visible Light Responsive Systems Based On Metastable-State Photoacids, Yi Liao

Chemistry and Chemical Engineering Faculty Publications

Proton transfer is one of the most fundamental processes in nature. Metastable-state photoacids can reversibly generate a large proton concentration under visible light with moderate intensity. which provides a general approach to control various proton transfer processes. Several applications of mPAHs have been demonstrated recently including control of acid-catalyzed reactions, volume-change of hydrogels, polymer conductivity, bacteria killing, odorant release, and color change of materials. They have also been utilized to control supramolecular assemblies, molecular switches, microbial fuel cells and cationic sensors. In this talk, the mechanism, structure design, and applications of metastable-state photoacids are introduced. Recent development of different types …

X-Ray Structure Of A Mammalian Stearoyl-Coa Desaturase, Yonghong Bai, Jason G. Mccoy, Elena J. Levin, Pablo Sobrado, Kanagalaghatta R. Rajashankar, Brian G. Fox, Ming Zhou

Chemistry Faculty Research & Creative Works

Stearoyl-CoA desaturase (SCD) is conserved in all eukaryotes and introduces the first double bond into saturated fatty acyl-CoAs. Because the monounsaturated products of SCD are key precursors of membrane phospholipids, cholesterol esters and triglycerides, SCD is pivotal in fatty acid metabolism. Humans have two SCD homologues (SCD1 and SCD5), while mice have four (SCD1-SCD4). SCD1-deficient mice do not become obese or diabetic when fed a high-fat diet because of improved lipid metabolic profiles and insulin sensitivity^5,6. Thus, SCD1 is a pharmacological target in the treatment of obesity, diabetes and other metabolic diseases⁷. SCD1 is an integral …

Applications Of Green Chemistry In Asymmetric Transfer Hydrogenation And Chiral Separations, Ruoqiu Wu

Seton Hall University Dissertations and Theses (ETDs)

Green chemistry has been applied to all aspects of the life cycle of chemically related products, including design, usage, manufacturing, analysis, and disposal. In this thesis, I focus on the green chemistry applications in organic synthesis and analytical chemistry. More specifically, allylic and chiral alcohols are abundant in natural sources such as in essential oils, and widely utilized as starting materials. They are also major components in food, fragrance, biocides and the pharmaceutical compounds. In this thesis, I report the first Ru-catalysed asymmetric transfer hydrogenation (ATH) of prochiral allylic alcohols. This reaction provides chiral secondary alcohols in excellent enantioselectivities and …

Biomass Burning Emissions And Potential Air Quality Impacts Of Volatile Organic Compounds And Other Trace Gases From Temperate Fuels Common In The United States, J. B. Gilman, B. M. Lerner, W. C. Kuster, P. D. Goldan, C. Warneke, P. R. Veres, J. M. Roberts, J. A. De Gouw, I. R. Burling, Robert Yokelson

Chemistry and Biochemistry Faculty Publications

A comprehensive suite of instruments was used to quantify the emissions of over 200 organic gases, including methane and volatile organic compounds (VOCs), and 9 inorganic gases from 56 laboratory burns of 18 different biomass fuel types common in the southeastern, southwestern, or northern United States. A gas chromatograph-mass spectrometer (GC-MS) provided extensive chemical detail of discrete air samples collected during a laboratory burn and was complemented by real-time measurements of organic and inorganic species via an open-path Fourier transform infrared spectrometer (OP-FTIR) and 3 different chemical ionization-mass spectrometers. These measurements were conducted in February 2009 at the U.S. Department …

Understanding The Interactions Of Carbon Nanotubes With Environmentally-Relevant Ions And Hydrogen Peroxide For Optical Sensing, Azhar Abdul Kareem Kamel

Theses and Dissertations

Single-walled carbon nanotubes (SWNTs) have drawn great attention in chemical and biological optical sensor applications due to their novel near infrared (NIR) optical properties that are extremely sensitive to the surrounding environment. This dissertation is devoted to four research areas: 1) Redox chemistry of sodium dodecyl sulfate (SDS)-encased SWNTs with mercuric ions in an aqueous environment for optical sensing: Various factors including SDS and SWNT concentrations, different pH levels, and buffer constituents, have been systematically examined. SWNTs show high selectivity and sensitivity to Hg2+ over eleven other metal ions. The determined detection limit is 0.6 nM, lower than 10.0 nM, …

Inhibition Of The Dape-Encoded N-Succinyl- ʟ, ʟ-Diaminopimelic Acid Desuccinylase From Neisseria Meningitidis By ʟ-Captopril, Anna Starus, Boguslaw Nocek, Brian Bennett, James A. Larrabee, Daniel L. Shaw, Wisath Sae-Lee, Marie T. Russo, Danuta M. Gillner, Magdalena Makowska-Grzyska, Andzrej Joachimiak, Richard C. Holz

Physics Faculty Research and Publications

Binding of the competitive inhibitor ʟ-captopril to the dapE-encoded N-succinyl-ʟ, ʟ-diaminopimelic acid desuccinylase from Neisseria meningitidis (NmDapE) was examined by kinetic, spectroscopic, and crystallographic methods. ʟ-Captopril, an angiotensin-converting enzyme (ACE) inhibitor, was previously shown to be a potent inhibitor of the DapE from Haemophilus influenzae (HiDapE) with an IC₅₀ of 3.3 μM and a measured K_i of 1.8 μM and displayed a dose-responsive antibiotic activity toward Escherichia coli. ʟ-Captopril is also a competitive inhibitor of NmDapE with a K_i of 2.8 μM. To examine the nature of the interaction …

Di- And Trinuclear Mixed-Valence Copper Amidinate Complexes From Reduction Of Iodine, Andrew C. Lane, Charles L. Barnes, William E. Antholine, Denan Wang, Adam T. Fiedler, Justin R. Walensky

Chemistry Faculty Research and Publications

Molecular examples of mixed-valence copper complexes through chemical oxidation are rare but invoked in the mechanism of substrate activation, especially oxygen, in copper-containing enzymes. To examine the cooperative chemistry between two metals in close proximity to each other we began studying the reactivity of a dinuclear Cu(I) amidinate complex. The reaction of [(2,6-Me2C6H3N)2C(H)]2Cu2, 1, with I2 in tetrahydrofuran (THF), CH3CN, and toluene affords three new mixed-valence copper complexes [(2,6-Me2C6H3N)2C(H)]2Cu2(μ2-I3)(THF)2, 2, [(2,6-Me2C6H3N)2C(H)]2Cu2(μ2-I) (NCMe)2, 3, and [(2,6-Me2C6H3N)2C(H)]3Cu3(μ3-I)2, 4, respectively. The first two compounds were characterized by UV-vis and electron paramagnetic resonance spectroscopies, and their molecular structure was determined by X-ray crystallography. Both …

Comparison Of Ch∙∙O, Sh∙∙O, Chalcogen, And Tetrel Bonds Formed By Neutral And Cationic Sulfur-Containing Compounds, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

The ability of neutral and charged S-compounds to form different sorts of noncovalent bonds is examined by ab initio calculations. Neutrals are represented by CH3SH and fluoro substituted FSCH3; cations are (CH3)3S+, CH3SH2+, and FHSCH3+. Each is paired with N-methylacetamide (NMA) whose O atom serves as common electron donor. Charged species engage in much stronger noncovalent bonds than do the neutral molecules, by as much as an order of magnitude. The strongest noncovalent bond for any system is a O∙∙SF chalcogen bond wherein the O lies directly opposite a S-F covalent bond, amounting to as much as 39 kcal/mol. Second …

Electrochemical Characterization Of Protein Adsorption Onto Yngrt-Au And Vlgxe-Au Surfaces, Hanna Trzeciakiewicz, Jose Esteves-Villanueva, Rania Soudy, Kamaljit Kaur, Sanela Martic-Milne

Pharmacy Faculty Articles and Research

The adsorption of the proteins CD13, mucin and bovine serum albumin on VLGXE-Au and YNGRT-Au interfaces was monitored by electrochemical impedance spectroscopy in the presence of [Fe(CN)6]3−/4−. The hydrophobicity of the Au surface was tailored using specific peptides, blocking agents and diluents. The combination of blocking agents (ethanolamine or n-butylamine) and diluents (hexanethiol or 2-mercaptoethanol) was used to prepare various peptide-modified Au surfaces. Protein adsorption onto the peptide-Au surfaces modified with the combination of n-butylamine and hexanethiol produced a dramatic decrease in the charge transfer resistance, Rct, for all three proteins. In contrast, polar peptide-surfaces induced a minimal change in …

Bio-Inspired Composite Hydrogels For Osteochondral Regenerative Engineering, Grant N. Gellert, Liangju Kuang, Chunhui Jiang, Nur P. Damayanti, Joseph Irudayaraj, Meng Deng

The Summer Undergraduate Research Fellowship (SURF) Symposium

Treatment of osteochondral defects encompassing injury or degeneration to both the articular cartilage as well as the underlying subchondral bone presents a significant medical challenge. Current treatment options including autografts and allografts suffer from limited availability and risk of immunogenicity, respectively. The long term goal of this work is to develop an integrated scaffold system for treatment of osteochondral defects via in situ regeneration of bone, cartilage and the bone-cartilage interface. Hydrogels composed of polymer networks swollen in water provide an attractive biomaterial platform for regeneration of cartilage. In the present study, we have developed a novel composite hydrogel consisting …

Deconstructing Cation-Pi Interactions: Understanding The Binding Energies Involved With Metal And Aromatic Amino Acid Residues, Jen E. Werner, Lyudmila V. Slipchenko, Yen Bui

The Summer Undergraduate Research Fellowship (SURF) Symposium

The Effective Fragment Potential (EFP) method is a computationally efficient technique for describing non-covalent interactions, such as hydrogen bonding and van der Waals forces. Cation-pi interactions are a type of non-covalent interactions and are thought to be important in biological processes, such as permittivity of ion channels. The goal of our work is to establish that the EFP method reliably describes the strength, directionality, and composition of cation-pi interactions. Optimal geometries were found for a series of biologically relevant cations (K⁺, Li⁺, Na⁺, Ca²⁺, and Mg²⁺) and aryl moieties appearing …

Soluble Amyloid-Beta 42 Aggregates Stimulate Cellular Inflammation Independent Of Cd47, Sanjib Karki

Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the accumulation and deposition of aggregated amyloid-β protein (Aβ). Most of the studies indicate that Aβ1-42) and Aβ(1-40) play an important role in the neurodegenerative pathology in AD. A critical component of AD pathology is inflammation, which results from the activation of glial cells around the Aβ deposits. The goal of my dissertation research was to determine the role of Aβ aggregation in microglia-triggered inflammation and identify cellular components that mediate the inflammatory response. CD47 is a cellular receptor found on the microglia surface and it has been proposed to have …

Comparative Sorption Of Methylene Blue Onto Hydrophobic Clays, Alvaro D. Sponza, Natalia J. Fernandez, David Yang, Karla A. Ortiz, Abel E. Navarro

Publications and Research

Chemical modifications of clay to remove methylene blue (MB) from aqueous solutions at room temperature were compared. Natural bentonite (NC) was modified by cation exchange with hexadecyltrimethylammonium chloride (HC), bencyltriethylammonium chloride (BC), and tetramethylammonium chloride (TC) to reverse the surface polarity of the hydrophilic bentonite. The adsorption of MB was studied and fitted by the adsorption theories of Langmuir, Freundlich, Dubinin-Radushkevich, and Temkin. Equilibrium parameters were calculated, indicating that chemical modification did not improve the adsorption, due to the electrostatic adsorption mechanism. Specific surface area was determined, reporting the following trend: NC > TC > BC > HC. Isotherms show that TC is …

Weak Interactions Between Salmonella Enterica Flhb And Other Flagellar Export Apparatus Proteins Govern Type Iii Secretion Dynamics, Jonathan L. Mcmurry, Tohru Minamino, Yukio Furukawa, Joshua W. Francis

Faculty Articles

The bacterial flagellum contains its own type III secretion apparatus that coordinates protein export with assembly at the distal end. While many interactions among export apparatus proteins have been reported, few have been examined with respect to the differential affinities and dynamic relationships that must govern the mechanism of export. FlhB, an integral membrane protein, plays critical roles in both export and the substrate specificity switching that occurs upon hook completion. Reported herein is the quantitative characterization of interactions between the cytoplasmic domain of FlhB (FlhBC) and other export apparatus proteins including FliK, FlhAC and FliI. FliK and FlhAC bound …

Polycations Xxii. Ru(Bpy)2l2 And Ru(Phen)2l2 Systems With Cationic 4,4’-Bipyridine Ligands: Syntheses, Characteristics, And Interactions With Dna, Jasmine Hatcher, Freida Zavurov, Leslie Babukutty, Thomas Strekas, Robert Engel

Publications and Research

Earlier efforts have been concerned with the association of Ruthenium octahedral complexes with DNA. Since the positively charged ruthenium species has been found to associate with the electron rich major groove of double-stranded DNA, it was proposed the addition of cationic sites on the ligands attached to ruthenium would facilitate such association. Thus, we have synthesized several series of octahedral ruthenium complexes bearing ligands having within themselves cationic sites. These have been investigated in their interaction with calf thymus DNA using fluorescence titration analysis. The introduction of the cationic ligands has been found to exhibit enhanced association of the ruthenium …

Evaluation Of 5 Μm Superficially Porous Particles For Capillary And Microfluidic Lc Columns, James Grinias, Robert T. Kennedy

College of Science & Mathematics Departmental Research

Large-size (4–5 µm) superficially porous particles yield lower plate heights (e.g., the minimal reduced plate height or h_min ≈ 1.5) than fully porous particles of a similar size when packed into large-bore columns. This property allows for better chromatographic performance without the higher pressures required for smaller particles. This study explores the use of such particles in microfluidic LC columns where materials and fitting pressure limits can constrain the size of particle used. The theoretically predicted performance improvements compared to fully porous particles were not demonstrated in capillary columns (with h_min ≈ 2 for both particle types), in …

Climatology And Atmospheric Chemistry Of The Non-Methane Hydrocarbons Ethane And Propane Over The North Atlantic, Detlev Helmig, Mauricio Muñoz, Jacques Hueber, Claudio Mazzoleni, Lynn Mazzoleni, Richard C. Owen, Maria Val-Martin, Paulo Fialho, Christian Plass-Duelmer, Paul I. Palmer, Alastair C. Lewis, Gabriele Pfister

Department of Chemistry Publications

A record spanning ten years of non-methane hydrocarbon (NMHC) data from the Pico Mountain Observatory (PMO), Pico Island, Azores, Portugal, was analyzed for seasonal NMHC behavior, atmospheric processing, and trends, focusing on ethane and propane. The location of this site in the central North Atlantic, at an elevation of 2225 m asl, allows these data to be used to investigate the background conditions and pollution transport events occurring in the lower free North Atlantic troposphere. The quantity ln([propane]/[ethane]) was used as an indicator of both photochemical processing and a marker for the occurrence of pollution transport events detected at the …

Scope And Mechanistic Analysis For Chemoselective Hydrogenolysis Of Carbonyl Compounds Catalyzed By A Cationic Ruthenium Hydride Complex With A Tunable Phenol Ligand, Nishantha Kumara Kalutharage, Chae S. Yi

Chemistry Faculty Research and Publications

A cationic ruthenium hydride complex, [(C₆H₆)(PCy₃)(CO)RuH]⁺BF₄^– (1), with a phenol ligand was found to exhibit high catalytic activity for the hydrogenolysis of carbonyl compounds to yield the corresponding aliphatic products. The catalytic method showed exceptionally high chemoselectivity toward the carbonyl reduction over alkene hydrogenation. Kinetic and spectroscopic studies revealed a strong electronic influence of the phenol ligand on the catalyst activity. The Hammett plot of the hydrogenolysis of 4-methoxyacetophenone displayed two opposite linear slopes for the catalytic system 1/p-X-C₆H₄OH (ρ = …

Ribosome Component Turnover Kinetics Describes A Two-Pool Kinetic Model In Dietary Restriction That Suggests Rpl10 Is Exchanged During Ribosome Lifespan, Andrew David Mathis

Theses and Dissertations

The eukaryotic ribosome is a large molecular machine consisting of ~80 ribosomal proteins and 4 rRNAs. The 40S and 60S ribosomal subunits are assembled in the nucleolus by ~200 helper proteins then shipped into the cytoplasm or to the endoplasmic reticulum where protein translation takes place. Eventually ribosomes are removed from the cytoplasm and recycled through ribophagy, however, very is little is known about ribosomal protein exchange after assembly but before ribophagy. Using kinetic turnover measurements of ribosomal proteins and rRNA in vivo we determined ribosomal protein replacement rates are diverse suggesting ribosomal components may be replaced without destruction of …

Metal-Free Tandem Beckmann–Electrophilic Aromatic Substitution Cascade Affording Diaryl Imines, Ketones, Amines, And Quinazolines, Samuel Sarsah, Marlon R. Lutz Jr., Kailyn Chichi Bobb, Daniel Becker

Chemistry: Faculty Publications and Other Works

A cascade reaction sequence involving a Beckmann rearrangement on benzophenone oxime followed by an electrophilic aromatic substitution (EAS) on the intermediate nitrilium ion affords N-phenyl diaryl imines that may then be hydrolyzed to ketones, or reduced to the corresponding amines. Reaction with benzonitrile afforded 2,4-diphenylquinazoline through a Beckmann–Ritter–EAS cascade.

Life’S Lessons In The Lab: A Summer Of Learning From Undergraduate Research Experiences, Louis S. Nadelson, Don Warner, Eric Brown

Chemistry and Biochemistry Faculty Publications and Presentations

Research experiences for undergraduates (REUs) seek to increase the participating students’ knowledge and perceptions of scientific research through engagement in laboratory research and related activities. Various REU outcomes have been investigated, including influence on participants’ content knowledge, career plans, and general perceptions of their domains of research. The complexity of REUs and dynamic nature of student development provide opportunity for exploring how REUs influence student growth. Our research focused on first and second-year college students who participated in a residential REU program that took place in a chemistry department in a metropolitan university in the western United States. We assessed …

Effects Of Allosteric Mutations On Dihydrofolate Reductase, Marian Okondo

Theses, Dissertations and Culminating Projects

Dihydrofolate reductase (DHFR) is an essential enzyme necessary in the synthesis of DNA precursors. DHFR acquires resistance to numerous known anti-folates and this has led to the continuous need to discover novel and selective DHFR inhibitors. Allosteric mutations on Bacillus stearothermophilus (Bs.) DHFR were previously found to alter inhibitor binding and specificity. In this work, we investigate how these mutations affect the conformational motions of DHFR associated with inhibitor binding. Two distal allosteric mutations, isoleucine at position 86 to alanine (I86A) and tyrosine at position 127 to alanine (Y127A) were separately introduced to C73A/S131C, a previously modified wild type DHFR …