A5007097283- Nuclear Structure and Function
- Protein Structure and Dynamics
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Robotic Path Planning Algorithms
- Enzyme Structure and Function
- Computational Geometry and Mesh Generation
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Chemical Synthesis and Analysis
- Diabetes Management and Research
- Microbial Metabolic Engineering and Bioproduction
- Pancreatic function and diabetes
- Radioactive element chemistry and processing
- Gene Regulatory Network Analysis
- Cellular Mechanics and Interactions
- RNA regulation and disease
- Mass Spectrometry Techniques and Applications
- Robotics and Sensor-Based Localization
- Software Testing and Debugging Techniques
- Teaching and Learning Programming
- Computational Drug Discovery Methods
- Genetic Neurodegenerative Diseases
- Single-cell and spatial transcriptomics
- Autonomous Vehicle Technology and Safety
University of California, San Francisco
2013-2024
Hebrew University of Jerusalem
2008-2024
Quantitative BioSciences
2021-2024
Rockefeller University
2018
QB3
2013-2018
Tel Aviv University
2008-2013
Hebrew College
2007-2010
Weizmann Institute of Science
2007
A wide range of regulatory processes in the cell are mediated by flexible peptides that fold upon binding to globular proteins. Computational efforts model these interactions hindered large number rotatable bonds relative typical ligand molecules, and fact different assume backbone conformations within same site. In this study, we present Rosetta FlexPepDock, a novel tool for refining coarse peptide-protein models allows significant changes both peptide side chains. We obtain high resolution...
Passive macromolecular diffusion through nuclear pore complexes (NPCs) is thought to decrease dramatically beyond a 30-60-kD size threshold. Using thousands of independent time-resolved fluorescence microscopy measurements in vivo, we show that the NPC lacks such firm threshold; instead, it forms soft barrier passive intensifies gradually with increasing molecular mass both wild-type and mutant strains various subsets phenylalanine-glycine (FG) domains different levels baseline permeability....
Peptide–protein interactions are among the most prevalent and important in cell, but a large fraction of those lack detailed structural characterization. The Rosetta FlexPepDock web server ( http://flexpepdock.furmanlab.cs.huji.ac.il/ ) provides an interface to high-resolution peptide docking (refinement) protocol for modeling peptide–protein complexes, implemented within framework. Given protein receptor structure approximate, possibly inaccurate model binding site, refines high resolution,...
Flexible peptides that fold upon binding to another protein molecule mediate a large number of regulatory interactions in the living cell and may provide highly specific recognition modules. We present Rosetta FlexPepDock ab-initio, protocol for simultaneous docking de-novo folding peptides, starting from an approximate specification peptide site. Using fragments library coarse-grained structural representation receptor, ab-initio samples efficiently simultaneously space possible backbone...
Abstract In this study, we assess on a large scale the possibility of deriving self‐inhibitory peptides from protein domains with globular architectures. Such inhibitory would inhibit interactions their origin domain by mimicking its mode binding to cognate partners, and could serve as promising leads for rational design drugs. For our large‐scale analysis, analyzed short linear segments that were cut out interfaces in silico complex structures protein–protein docking Benchmark 3.0 CAPRI...
Significance The nuclear pore complex (NPC) mediates the trafficking of macromolecules in and out nucleus eukaryotic cells. Here, we characterize how transport factors diffuse rapidly through multiple layers disordered phenylalanine-glycine (FG) repeat domains lining NPC. Transport interact with FG repeats a dynamic sliding motion, enabling faster translocation NPC than that attainable by two-state binding mechanism as well effectively blocking passage large do not bind to factors. Thus,...
Chemokines orchestrate cell migration for development, immune surveillance, and disease by binding to surface heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). The array of interactions between the nearly 50 chemokines their 20 GPCR targets generates an extensive signaling network which promiscuity biased agonism add further complexity. receptor CXCR4 recognizes both monomeric dimeric forms chemokine CXCL12, is a distinct example ligand bias in family....
Abstract Metal ions are crucial for protein function. They participate in enzyme catalysis, play regulatory roles, and help maintain structure. Current tools predicting metal–protein interactions based on proteins crystallized with their metal present (holo forms). However, a majority of resolved structures free (apo Moreover, binding is dynamic process, often involving conformational rearrangement the pocket. Thus, effective predictions need to be structure apo state. Here, we report an...
Abstract Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport of specific macromolecules while impeding the exchange unsolicited material. However, key aspects this gating mechanism remain controversial. To address issue, we determined nanoscopic behavior permeability barrier directly within yeast S. cerevisiae NPCs at transport-relevant timescales. We show that large intrinsically disordered domains phenylalanine-glycine repeat nucleoporins (FG Nups) exhibit highly dynamic...
Sampling-based motion planners are an effective means to generate collision-free paths. However, the quality of these paths (with respect measures, such as path length, clearance, smoothness, or energy) is often notoriously low, especially in high-dimensional configuration spaces. We introduce a simple algorithm merge arbitrary number input into hybrid output superior quality, for broad and general formulation quality. Our approach based on observation that certain subpaths within each...
The Nuclear Pore Complex (NPC) facilitates rapid and selective nucleocytoplasmic transport of molecules as large ribosomal subunits viral capsids. It is not clear how key emergent properties this arise from the system components their interactions. To address question, we constructed an integrative coarse-grained Brownian dynamics model through a single NPC, followed by coupling it with kinetic Ran-dependent in entire cell. microscopic parameters were fitted to reflect experimental data...
Proteins are active, flexible machines that perform a range of different functions. Innovative experimental approaches may now provide limited partial information about conformational changes along motion pathways proteins. There is therefore need for computational can efficiently incorporate prior into prediction schemes. In this paper, we present PathRover, general setup designed the integration planning algorithm rapidly exploring random trees (RRT). Each suggested pathway comprises...
Significance Cells are the basic units of life, yet their architecture and function remain to be fully characterized. This work describes Bayesian metamodeling, a modeling approach that divides conquers large problem numerous aspects cell into computing number smaller models different types, followed by assembling these complete map cell. Metamodeling enables facile collaboration multiple research groups communities, thus maximizing sharing expertise, resources, data, models. A proof...
We have recently reported drug-releasing, degradable Tetra-PEG hydrogels as a new drug delivery system. The gels contain two self-cleaving β-eliminative linkers: one that covalently tethers the to gel and releases it at predictable rate, another with slower cleavage is installed in each cross-link of polymer control degradation. By balancing rates, system can be designed discharge most or all before undergoes significant If degradation too rapid, undesirable gel-fragments bound are released;...
Glycogen synthase kinase 3β (GSK-3β) is a serine-threonine belonging to the CMGC family that plays key role in many biological processes, such as glucose metabolism, cell cycle regulation, and proliferation. Like most protein kinases, GSK-3β regulated via multiple pathways sites. We performed all-atom molecular dynamics simulations on unphosphorylated phosphorylated unbound bound peptide substrate, its product, derived inhibitor. found autophosphorylation at residue Tyr(216) results widening...
Dictyostelium discoideum myosin II heavy chain kinase A (MHCK A), a member of the atypical α-kinase family, phosphorylates sites in tail that block filament assembly. Here we show catalytic activity A-CAT, domain MHCK (residues 552–841), is severely inhibited by removal disordered C-terminal sequence (C-tail; residues 806–841). The key residue C-tail was identified as Thr825, which found to be constitutively autophosphorylated. Dephosphorylation Thr825 using shrimp alkaline phosphatase...