Browsing Biological chemistry by Title
Now showing items 24-43 of 122
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Conditional Generation of Protein Sequence and Structure
The advent of atomic accuracy protein sequence structure prediction with deep learning networks spurred by AlphaFold has had a remarkable impact on the field of biochemistry. It has resulted in rapid progress in protein ... -
CONTROL OF RAB SMALL G-PROTEINS IN YEAST ENDOSOMAL TRAFFIC
(2013-07-25)The protein trafficking pathway in eukaryotic cells is essential for maintenance of organelle identity, nutrient uptake, and adaptation to extracellular stimuli. The endocytic pathway is tasked with uptake of plasma membrane ... -
De Novo Design of Bioactive Protein Switches, and Applications Thereof
Allosteric regulation of protein function is widespread in biology, but challenging for de novo protein design as it requires explicit design of multiple states with comparable free energies. We explore the possibility of ... -
De Novo Design of Buttressed Loops for Diversifying Protein Functions
Loops play essential roles in protein functions such as protein-protein interactions, ligand recognition and metal binding. However, designing structured and functional loops remains to be a long-standing challenge for ... -
De novo design of obligate ABC heterotrimeric proteins
The self-association of three distinct proteins, or essentially an ABC heterotrimer, is seen in a few instances in nature but the challenge of designing cooperative 3-sided interfaces has not been tackled yet in the field ... -
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 ... -
De Novo Design of Protein Nanoparticles with Programmable and Tunable Function
Assembly of designed symmetric protein nanoparticles from multiple copies of one or more distinct protein subunits warrants unique shapes, size diversity, structural regularity, and polyvalency. Current efforts of protein ... -
De Novo Design of Pseudosymmetric Protein Hetero-Oligomers
Protein design success is considerably higher now than it has been in the recent past, but the simultaneous design of many complex interactions, such as hetero-oligomers, remains difficult. We developed a strategy for ... -
De novo model building with cryo-EM density and coevolution restraints
Low-resolution limitations have long plagued cryo-EM de novo modeling. To address this challenge, I modified Rosetta de novo to incorporate fragments with tertiary context, or nonlocal fragments. Limitations I identified ... -
De novo protein fusions as platforms for enzyme design
Control over enzymatic catalysis is a central goal of biotechnology. Recent advances in computational protein design are beginning to allow for the de novo creation of arbitrary protein structures, but the design of arbitrary ... -
De Novo Scaffold Design: From Membrane β-Barrels to ɑ-helical Repeat Oligomers
De novo design of new protein folds, shapes, and features opens up new avenues for functional design. My thesis work covers the de novo design of membrane beta barrels, important considerations for making new metal binding ... -
Defining Protein Interactions With Small Heat Shock Proteins
Small heat shock proteins (sHSPs) are a class of molecular chaperones broadly observed across organisms where they play a central role in maintaining protein homeostasis under conditions of cellular stress. sHSPs are known ... -
Design of a hyperstable 60-subunit icosahedral nanocage
The icosahedron is the largest of the Platonic solids, and icosahedral protein structures are widely used in biological systems for packaging and transport1,2. There has been considerable interest in repurposing such ... -
Design of De Novo Mimetic Protein of Interleukin-21 and Its Therapeutic Efficacy in Cancer
Interleukin-21 (IL-21) is crucial in coordinating immune cells and has pleiotropic effects in their immune responses. It has established clinical anti-tumor activity for melanoma, non-Hodgkin’s lymphoma, and renal cell ... -
Design of De Novo Mini Fluorescence Activating Proteins as pH and Calcium Biosensors
Recent advances in de novo protein design have enabled the design of mini fluorescence activating proteins (mFAPs): mini β-barrel topologies that bind and stabilize the fluorescent cis-planar state of the fluorogenic ... -
Designed proteins assemble antibodies into modular nanocages
Antibodies are widely used in biology and medicine, and there has been considerable interest in multivalent antibody formats that increase binding avidity and enhance signaling. However, general approaches are lacking for ... -
Development and validation of statistical potential functions for the prediction of protein/nucleic-acid interactions from structure
(2007)This work outlines the development, validation and application of a series of novel statistical (knowledge-based) potential functions to the prediction of protein/nucleic-acid interactions from structure. Three methods are ... -
Development of a Novel Gene Therapy & Investigation of Synthetic Gene Therapy Delivery Systems
Dystroglycanopathies are a family of neuromuscular disorders, in which enzymes that glycosylate the protein dystroglycan and therefore play a key role in muscle structure, have reduced or nonexistent activity. For example, ... -
Development of Automated Methods for Modeling Ligands in Cryo-Electron Microscopy Data
Advances in cryo-electron microscopy (cryoEM) and deep-learning guided protein structure prediction have expedited structural studies of protein complexes. However, methods for accurately modeling ligand conformations are ... -
Development of Tools for the Interpretation of Cryo-EM Data
In this dissertation, I describe my efforts to build tools to address two gaps in the field of cryo-electron microscopy: deriving structural details about the conformational landscape from cryo-EM data and model validation ...