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Articles 1 - 5 of 5
Full-Text Articles in Physical Sciences and Mathematics
Machine Learning Applications For Drug Repurposing, Hansaim Lim
Machine Learning Applications For Drug Repurposing, Hansaim Lim
Dissertations, Theses, and Capstone Projects
The cost of bringing a drug to market is astounding and the failure rate is intimidating. Drug discovery has been of limited success under the conventional reductionist model of one-drug-one-gene-one-disease paradigm, where a single disease-associated gene is identified and a molecular binder to the specific target is subsequently designed. Under the simplistic paradigm of drug discovery, a drug molecule is assumed to interact only with the intended on-target. However, small molecular drugs often interact with multiple targets, and those off-target interactions are not considered under the conventional paradigm. As a result, drug-induced side effects and adverse reactions are often neglected …
Small Molecule Synthetic Carbohydrate Receptors, Marcelo F. Bravo Carranco
Small Molecule Synthetic Carbohydrate Receptors, Marcelo F. Bravo Carranco
Dissertations, Theses, and Capstone Projects
Carbohydrate – receptor interactions are often involved in the attachment of viruses to host cells, and this docking is a necessary step in the virus life cycle that precedes infection and, ultimately, replication. Despite the conserved structures of the glycans involved in docking, they are still considered “undruggable”, meaning these glycans are beyond the scope of conventional pharmacological strategies. Recent advances in the development of synthetic carbohydrate receptors (SCRs) – small molecules that bind carbohydrates – could bring carbohydrate-receptor interactions within the purview of druggable targets. Here we discuss the role of carbohydrate-receptor interactions in viral infection, the evolution of …
Pointing The Zinc Finger On Protein Folding: Energetic Investigation Into The Role Of The Metal-Ion In The Metal-Induced Protein Folding Of Zinc Finger Motifs, Inna Bakman-Sanchez
Pointing The Zinc Finger On Protein Folding: Energetic Investigation Into The Role Of The Metal-Ion In The Metal-Induced Protein Folding Of Zinc Finger Motifs, Inna Bakman-Sanchez
Dissertations, Theses, and Capstone Projects
Interactions between inorganic metal-ion cofactors and organic protein scaffolds are important for the proper structure and function of metalloproteins. Zinc finger proteins (ZFPs) are an example of proteins with such crucial metal-protein interactions. Incorporation of the Zn(II)-ion into ZFPs allows for their correct folding into structures that can carry out vital biological functions which include gene expression and tumor suppression. In addition, engineered ZFPs have shown to be promising genetic therapeutics in the clinic. And yet, there is still a gap in a quantitative understanding of the energetic contribution of the metal-protein interactions towards the structure and function of these …
Advanced Computational Methodologies To Study Binding Free Energies Of Biomolecular Complexes, Rajat Kumar Pal
Advanced Computational Methodologies To Study Binding Free Energies Of Biomolecular Complexes, Rajat Kumar Pal
Dissertations, Theses, and Capstone Projects
Molecular recognition is the basis of biological mechanisms and is a key element to consider while formulating effective and safe drugs. Pharmaceutical drugs are designed so as to bind a target protein even at very low concentrations to alter the diseased conditions without interfering with normal biological processes. In a rational drug design process, this is achieved by acquiring information about the chemical structure and the physical and chemical properties of the target protein receptor to gain insights on how changing the chemical composition of the substrate drug could affect the protein-drug interaction and binding affinities. Computational models are used …
Leveraging Antibodies For Positron Emission Tomography And Near-Infrared Fluorescence Imaging Of Cancer, Kimberly C. Fung
Leveraging Antibodies For Positron Emission Tomography And Near-Infrared Fluorescence Imaging Of Cancer, Kimberly C. Fung
Dissertations, Theses, and Capstone Projects
The high specificity and affinity of antibodies make them attractive for developing drugs to diagnose and treat cancer. The overarching goal of this work is to explore the synthesis and use of antibody-based imaging agents in preclinical models of cancer. This work can be described as two-fold. In the first part, we investigated how the use of a glycans-specific bioconjugation strategy affects Fc gamma RI binding and why it results in improved in vivo performance of immunoconjugates. To do so, we used the clinically relevant positron emission tomography (PET) imaging agent, 89Zr-DFO-pertuzumab, in mouse models of human breast cancer. …