- RNA and protein synthesis mechanisms
- Advanced Proteomics Techniques and Applications
- Bioinformatics and Genomic Networks
- Genomics and Phylogenetic Studies
- RNA Research and Splicing
- Hemoglobin structure and function
- Erythrocyte Function and Pathophysiology
- Blood properties and coagulation
- Chemical Synthesis and Analysis
- RNA modifications and cancer
- Machine Learning in Bioinformatics
- Genetic and Kidney Cyst Diseases
- Biochemical and Structural Characterization
- Protein Structure and Dynamics
- Microtubule and mitosis dynamics
- Protist diversity and phylogeny
- Mass Spectrometry Techniques and Applications
- Enzyme Structure and Function
- Genetics, Aging, and Longevity in Model Organisms
- Advanced Electron Microscopy Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Microbial Community Ecology and Physiology
- Glycosylation and Glycoproteins Research
- Amino Acid Enzymes and Metabolism
- Genetics, Bioinformatics, and Biomedical Research
University of Illinois Chicago
2021-2024
Ashland (United States)
2022
The University of Texas at Austin
2014-2021
New York University
2006-2017
University of Washington
2016
Washington Center
2016
Courant Institute of Mathematical Sciences
2006-2009
University of Augsburg
2008
DePaul University
2007
Manaaki Whenua – Landcare Research
2003
The Rosetta molecular modeling software package provides experimentally tested and rapidly evolving tools for the 3D structure prediction high-resolution design of proteins, nucleic acids, a growing number non-natural polymers. Despite its free availability to academic users improving documentation, use has largely remained confined developers their immediate collaborators due code's difficulty use, requirement large computational resources, unavailability servers most applications. Here, we...
Abstract Macromolecular protein complexes carry out many of the essential functions cells, and genetic diseases arise from disrupting such complexes. Currently, there is great interest in defining complete set human complexes, but recent published maps lack comprehensive coverage. Here, through synthesis over 9,000 mass spectrometry experiments, we present hu. MAP , most accurate complex map to date, containing > 4,600 total 7,700 proteins, 56,000 unique interactions, including thousands...
A general principle of biology is the self-assembly proteins into functional complexes. Characterizing their composition is, therefore, required for our understanding cellular functions. Unfortunately, we lack knowledge comprehensive set identities protein complexes in human cells. To address this gap, developed a machine learning framework to identify over 15,000 mass spectrometry experiments which resulted identification nearly 7,000 physical assemblies. We show resource, hu.MAP 2.0, more...
Protein–protein interactions encompass large surface areas, but often a handful of key residues dominate the binding energy landscape. Rationally designed small molecule scaffolds that reproduce relative positioning and disposition important residues, termed "hotspot residues", have been shown to successfully inhibit specific protein complexes. Although this strategy has led development novel synthetic inhibitors complexes, direct mimicry natural amino acid does not lead potent inhibitors....
Red blood cells (RBCs) (erythrocytes) are the simplest primary human cells, lacking nuclei and major organelles instead employing about a thousand proteins to dynamically control cellular function morphology in response physiological cues. In this study, we define canonical RBC proteome interactome using quantitative mass spectrometry machine learning. Our data reveal an dominated by protein homeostasis, redox biology, cytoskeletal dynamics, carbon metabolism. We validate complexes through...
RNA-binding proteins (RBPs) play essential roles in biology and are frequently associated with human disease. Although recent studies have systematically identified individual proteins, their higher-order assembly into ribonucleoprotein (RNP) complexes has not been investigated. Here, we describe a proteomics method for systematic identification of RNP cells. We identify 1,428 protein that associate RNA, indicating more than 20% known contain RNA. To explore the role RNA each complex,...
Endospores formed by Bacillus subtilis are encased in a tough protein shell known as the coat, which consists of at least 70 different proteins. We investigated process spore coat morphogenesis using library 40 proteins fused to green fluorescent and demonstrate that two successive steps can be distinguished assembly. The first step, initial localization surface, is dependent on morphogenetic SpoIVA SpoVM. second encasement, requires third protein, SpoVID. show spoVID mutant cells, most...
Peptidomimetics are classes of molecules that mimic structural and functional attributes polypeptides. Peptidomimetic oligomers can frequently be synthesized using efficient solid phase synthesis procedures similar to peptide synthesis. Conformationally ordered peptidomimetic finding broad applications for molecular recognition inhibiting protein-protein interactions. One critical limitation is the limited set design tools identifying oligomer sequences adopt desired conformations. Here, we...
Ciliary motility is driven by axonemal dyneins that are assembled in the cytoplasm before deployment to cilia. Motile ciliopathy can result from defects themselves or factors required for their cytoplasmic pre-assembly. Recent work demonstrates dyneins, specific assembly factors, and broadly-acting chaperones concentrated liquid-like organelles called DynAPs (Dynein Axonemal Particles). Here, we use
Abstract BioNetBuilder is an open-source client-server Cytoscape plugin that offers a user-friendly interface to create biological networks integrated from several databases. Users can for ∼1500 organisms, including common model organisms and human. Currently supported databases include: DIP, BIND, Prolinks, KEGG, HPRD, The BioGrid GO, among others. client available as Java Webstart, providing platform-independent network these public Availability: Contact: iliana_avila-campillo@merck.com
The incompleteness of proteome structure and function annotation is a critical problem for biologists and, in particular, severely limits interpretation high-throughput next-generation experiments. We have developed pipeline based on prediction, where annotations are generated using an integration sequence comparison, fold recognition, grid-computing-enabled de novo prediction. predict protein domain boundaries three-dimensional (3D) structures domains from 94 genomes (including human,...
Multi-protein complexes are necessary for nearly all cellular processes, and understanding their structure is required elucidating function. Current high-resolution strategies in structural biology effective but lag behind other fields (e.g., genomics proteomics) due to reliance on purified samples rather than heterogeneous mixtures. Here, we present a method combining single-particle analysis by electron microscopy with protein identification mass spectrometry structurally characterize...
Abstract Background Systems Biology research tools, such as Cytoscape, have greatly extended the reach of genomic research. By providing platforms to integrate data with molecular interaction networks, researchers can more rapidly begin interpretation large sets collected for a system interest. BioNetBuilder is an open-source client-server Cytoscape plugin that automatically integrates interactions from all major public databases and serves them directly user's environment. Until recently...
Abstract Motivation: Computational biologists have demonstrated the utility of using machine learning methods to predict protein function from an integration multiple genome-wide data types. Yet, even best performing prediction algorithms rely on heuristics for important components algorithm, such as choosing negative examples (proteins without a given function) or determining key parameters. The improper choice examples, in particular, can hamper accuracy prediction. Results: We present...
Protein phosphorylation is a key regulatory mechanism involved in nearly every eukaryotic cellular process. Increasingly sensitive mass spectrometry approaches have identified hundreds of thousands sites, but the functions vast majority these sites remain unknown, with fewer than 5% currently assigned function. To increase our understanding functional protein we developed an approach (phospho-DIFFRAC) for identifying phosphorylation-dependence assemblies systematic manner. A combination...
Co-fractionation/mass spectrometry (CF/MS) is a flexible and powerful method to detect physical associations of proteins. CF/MS can be applied any tissue or organism without the need for protein-specific antibodies epitope tags. Here, we outline two alternate protocols MS preparation samples (containing low high salt) computational pipeline (cfmsflow) that together allow successful application this approach. These are based on over 16 diverse organisms including plants animals. For complete...
Determining the three dimensional arrangement of proteins in a complex is highly beneficial for uncovering mechanistic function and interpreting genetic variation coding genes comprising protein complexes. There are several methods determining co-complex interactions between proteins, among them co-fractionation / mass spectrometry (CF-MS), but it remains difficult to identify directly contacting subunits within multi-protein complex. Correlation analysis CF-MS profiles shows promise...