Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 23 for “"De Novo Design"”.
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De novo design of protein binders as functional therapeutics
De novo design of protein binding proteins (minibinders) with target structure information alone remains a grand challenge. A general computational design framework includes (1) generation of binder backbones, (2) sequence design and side-chain refinement, (3) resampling, and (4) prediction of …
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De Novo Design of secondary structures: Synthesis and conformational studies
… unique in their ability to adopt compact, well-ordered conformations, and specific folding provides precise spatial orientation of the functional groups that comprise the “active site”. These features suggest that identification of new polymer backbones with discrete and predictable folding …
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DE NOVO DESIGN OF ANTIMICROBIAL PEPTIDES FOR APPLICATION AS ANTI-INFECTIVE AGENTS
Antimicrobial peptides (AMPs) have gathered considerable interest as a new source of antibiotics to tackle the escalating threat of antimicrobial resistance. Adopting a de novo approach enables the rational design of short synthetic AMPs, whilst mitigating concerns of resistance development to …
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In silico redesign and de novo design of anti-MUC1 monoclonal antibodies
… pathways which promote tumor growth and provides a suitable target for detection and treatment of epithelial cancers via antibodies. While anti-MUC1 monoclonal antibodies do exist, none have proven to be effective in clinical trials. Antibody fragments have been identified as possible …
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Investigating protein folding by the de novo design of an α-helix oligomer
… of a unique sequence of amino acids, whose order guides a protein to adopt its particular fold and perform a specific function. It has been shown that a protein's 3-dimensional structure is embedded within its primary sequence. The problem that remains elusive to biochemists is how a protein's …
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De Novo Design And Engineering Of Functional Metal And Porphyrin-Binding Protein Domains
<p>In this work, I describe an approach to the rational, iterative design and characterization of two functional cofactor-binding protein domains. First, a hybrid computational/experimental method was developed with the aim of algorithmically generating a suite of porphyrin-binding protein …
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De Novo Design and Stabilization of β-Sheet Peptides for Biomimicry of ORR Enzymes
This dissertation presents the de novo design of novel peptide-based materials that mimic the structure and function of the laccase enzyme, with a focus on applications in energy conversion technologies. Laccase is of particular interest due to its ability to catalyze the four-electron reduction of …
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De novo Design of Mini-Protein Binders Targeting Allosteric Sites of MALT1 Towards Cancer Therapeutics
… αναπτύξαμε μια in silico εκστρατεία σχεδιασμού de novo μικρών πρωτεϊνικών προσδετών στοχεύοντας δύο δομικά και λειτουργικά διακριτές αλλοστερικές θέσεις στην ανθρώπινη MALT1: τη Θέση 1 στην επιφάνεια της δομικής επικράτειας παρακασπάσης (PDB: 3V55, apo διαμόρφωση, hotspots V395, L440, I445, …
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De novo design of passively permeable cyclic peptides and incorporation of noncanonical amino acids to improve predicted binding affinity
Cyclic peptides fill an intermediate niche between traditional small molecule therapeutics and larger biologics. In ideal cases they combine the passive permeability and oral availability of small molecules with the binding specificity of larger biologics. However, achieving both of these features …
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Design, Synthesis, And Evaluation Of Molecular Inhibitors For Biologically Relevant Enzymes
<p>The work in this thesis details the design, synthesis, and biological evaluation of molecular inhibitors for the inhibition of biologically relevant enzymes. The first three chapters of this thesis concern the polyphenol resveratrol and its inhibition of the quinone reductase 2 (QR2) enzyme. The …
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Toward a Database of Geometric Interrelationships of Protein Secondary Structure Elements for De Novo Protein Design, Prediction and Analysis
… methods of analyzing, simulating, and modeling proteins are essential towards understanding protein structure and its interactions. Computational methods are easier as not all protein structures can be determined experimentally due to the inherent difficultly of working with some …
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Integrin-independent activation of Tie2 using the de novo designed protein H8mb
… it therapeutically have been limited by the poor developability and receptor promiscuity of Angiopoietin-1 (Ang1), which binds both Tie2 and α5β1 integrin. Here we report the de novo design of a compact Tie2 binding protein that overcomes these constraints. We use RFdiffusion to design a stable, …
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Advancement in In-Silico Drug Discovery from Virtual Screening Molecular Dockings to De-Novo Drug Design Transformer-based Generative AI and Reinforcement Learning
… seen remarkable advancements over the past few decades, transitioning from traditional experimental methods to highly sophisticated computational approaches. One of the pivotal techniques in this evolution is virtual screening, which utilizes molecular docking to predict the interaction between …
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Designing Macromolecules using Machine Learning and Simulations
… However, such chemical diversity hinders the development of general computational approaches that can be applied to macromolecules. The challenges around representing, comparing and learning over macromolecules are manifold. Current representations provide limited coverage of chemical …
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Toward accurate free energy calculations in biomolecular simulation: advances in Markov model reweighting and expanded ensemble method
The rational design of stable, preorganized peptides/ligands demands precise atomistic insights into their folded and unfolded conformational ensembles, which are often challenging to obtain from simulations alone due to timescale limitations and force field inaccuracies. This dissertation advances …
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Discovery of high quality molecular leads and screening collections for CNS drug targets
… an increasing area of unmet medical need. Despite high levels of investment from the pharmaceutical industry few disease modifying drugs have been discovered with the most common cause of late stage clinical failure being a lack of efficacy. In order to enable greater understanding of …
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Intrinsically Disordered Protein Polymer Libraries as Tools to Understand Protein Hydrophobicity
<p>Intrinsically disordered protein polymers (IDPPs) are repetitive biopolymers that, when enriched with prolines, glycines, and aliphatic amino acids, have observable lower critical solution temperature (LCST) phase transition behavior at physiologically relevant temperature and concentration …
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Computational methods for the structure-based design of protein-binding peptides
The de novo design of peptides that bind to target proteins could enable binding to specific epitopes, inhibition of natural interactions, and targeted degradation of proteins. Despite advances in protein engineering, this remains a challenging task due to the large space of peptide structures and …
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Design of Nuclear-Targeting Peptides for Macromolecule Delivery via Machine Learning
The effective design of functional peptide sequences remains a fundamental challenge in biomedicine. For example, cell-penetrating peptides (CPPs) are capable of delivering macromolecular cargo to intracellular targets that are otherwise inaccessible. However, design of novel CPPs with high …
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Investigating "difficult-to-express" monoclonal antibody frameworks in transient and site-specific integration-based Chinese hamster ovary cell expression systems
… of a monoclonal antibody (mAb) product is dependent on both its clinical performance and its “developability” profile, a set of characteristics that defines its ability to be manufactured at large-scale using current practices in the biopharmaceutical industry. Failure to identify low …
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