A5079187925- Protein Structure and Dynamics
- Alzheimer's disease research and treatments
- RNA Research and Splicing
- Enzyme Structure and Function
- Prion Diseases and Protein Misfolding
- RNA modifications and cancer
- Crystallization and Solubility Studies
- Protein purification and stability
- Material Dynamics and Properties
- RNA and protein synthesis mechanisms
- Lipid metabolism and biosynthesis
- Spectroscopy and Quantum Chemical Studies
- nanoparticles nucleation surface interactions
- Modular Robots and Swarm Intelligence
- Nanopore and Nanochannel Transport Studies
- Supramolecular Self-Assembly in Materials
- Surfactants and Colloidal Systems
- Monoclonal and Polyclonal Antibodies Research
- Bioinformatics and Genomic Networks
- Ubiquitin and proteasome pathways
- Computational Drug Discovery Methods
- Diffusion and Search Dynamics
- Molecular Junctions and Nanostructures
- Pickering emulsions and particle stabilization
- Synthesis and properties of polymers
Kansas State University
2016-2025
Chinese Academy of Sciences
2016
Institute of Physics
2016
University of California, San Francisco
2010-2012
University of California, Santa Barbara
2002-2010
Brandeis University
2007-2009
What are the physical limits to cell behavior? Often, limitations can be dominated by proteome, cell’s complement of proteins. We combine known protein sizes, stabilities, and rates folding diffusion, with protein-length distributions P ( N ) proteomes Escherichia coli , yeast, worm), formulate scaling relationships in order address questions physics. Why do mesophilic cells die around 50 °C? How maximal growth-rate temperature (around 37 °C) occur so close cell-death temperature? The model...
Abstract The formation of biomolecular condensates through phase separation from proteins and nucleic acids is emerging as a spatial organisational principle used broadly by living cells. Many such are not, however, homogeneous fluids, but possess an internal structure consisting distinct sub-compartments with different compositions. Notably, can contain compartments that depleted in the biopolymers make up condensate. Here, we show double-emulsion emerge via dynamically arrested...
Biomolecules associate, forming condensates that house essential biochemical processes, including ribosome biogenesis. Unraveling how shape macromolecular assembly and transport requires cellular measurements of nanoscale structure. Here, we determine the organization around between specific proteins at nanometer resolution within condensates, deploying thermodynamic principles to interpret partitioning designed protein probes. When applied nucleolus as a proof principle, data reveals...
Self-assembly of proteins into amyloid fibrils plays a key role in multitude human disorders that range from Alzheimer's disease to type II diabetes. Compact oligomeric species, observed early during formation, are reported as the molecular entities responsible for toxic effects self-assembly. However, relation between early-stage aggregates and late-stage rigid fibrils, which hallmark structure plaques, has remained unclear. We show these different structures occupy well-defined regions...
An accurate depiction of electrostatic interactions in molecular dynamics requires the correct number ions simulation box to capture screening effects. However, that should be added is seldom given by bulk salt concentration because a charged biomolecule solute will perturb local solvent environment. We present simple method for calculating only total charge, volume, and as inputs. show most commonly used adding results an effective too high. These findings are confirmed using simulations...
Biomolecular condensates are emerging as an important organizational principle within living cells. These condensed states formed by phase separation, yet little is known about how material properties encoded the constituent molecules and specificity for being in different phases established. Here we use analytic theory to explain behavior of cancer-related protein SPOP its substrate DAXX. Binary mixtures these have a diagram that contains dilute liquid, dense gel states. We show discrete...
Antibody solutions are typically much more viscous than of globular proteins at equivalent volume fraction. Here we propose that this is due to molecular entanglements caused by the elongated shape and intrinsic flexibility antibody molecules. We present a simple theory in which antibodies modeled as linear polymers can grow via reversible bonds between antigen binding domains. This mechanism explains observation relatively subtle changes interparticle interaction lead large viscosity. The...
Atomistic description of protein fibril formation has been elusive due to the complexity and long time scales conformational search. Here, we develop a multiscale approach combining numerous atomistic simulations in explicit solvent construct Markov State Models (MSMs) growth. The search for in-register fully bound state is modeled as random walk on rugged two-dimensional energy landscape defined by β-sheet alignment hydrogen-bonding states, whereas transitions involving states without...
Biomolecular condensates appear throughout the cell serving a wide variety of functions. Many to form by assembly multivalent molecules, which produce phase-separated networks with liquidlike properties. These then recruit client total composition providing functionality. Here we use model system poly-SUMO and poly-SIM proteins understand client-network interactions find that structure network plays strong role in defining recruitment thus The basic unit this is zipperlike filament composed...
Biomolecular condensates form via multivalent interactions among key macromolecules and are regulated through ligand binding and/or posttranslational modifications. One such modification is ubiquitination, the covalent addition of ubiquitin (Ub) or polyubiquitin chains to target macromolecules. Specific between partner proteins, including hHR23B, NEMO, UBQLN2, regulate condensate assembly disassembly. Here, we used a library designed hubs UBQLN2 as model systems for determining driving...
The nucleation of amyloid fibrils from monomeric protein, catalyzed by the surface existing fibrils, is an important driver many disorders such as Alzheimer's and Parkinson's diseases. structural basis this secondary process, however, poorly understood. Here, we ask whether sites are found predominantly at rare growth defects: defects in fibril core structure generated during their original assembly. We first demonstrate using specific inhibitor nucleation, Brichos, that on...
Phase-separated biomolecular condensates serve as functional elements of biological cells, contributors to the formation protocells in prebiotic systems during early life, and a distinct form material with range applications. Regulation condensate mechanochemistry is critical importance for their functions properties. Photochemical processes, such UV-induced chemical changes, are commonly observed nature can have both detrimental constructive impacts on also readily implemented engineering...
Protein crystallization is important for structural biology. The rate at which a protein crystallizes often the bottleneck in determining protein's structure. Here, we give physical model growth rates of crystals. Most materials crystallize faster under stronger conditions; however, slows down strongest conditions. Proteins require slot 'just right' Our provides an explanation. Unlike simpler materials, proteins are orientationally asymmetrical. Under strong conditions, molecules attempt to...
We use analytic theory and computer simulation to study patterns formed during the growth of two-component assemblies in two three dimensions. show that these undergo a nonequilibrium phase transition, at particular rate, between mixed demixed arrangements component types. This finding suggests principles statistical mechanics can be used predict outcome multicomponent self-assembly, an experimental route self-assembly structures qualitatively defined nature.
We study the effect of confinement on diffusion-limited bimolecular reactions within a lattice model where small number reactants diffuse among much larger inert particles. When particles is held constant, rate reaction slow for volumes due to limited mobility from crowding and large reduced concentration reactants. The proceeds fastest at an intermediate corresponding volume fraction near 50%. generalize off-lattice systems with hydrodynamic coupling predict that optimal monodisperse...
The growth of amyloid fibrils requires a disordered or partially unfolded protein to bind the fibril and adapt same conformation alignment established by template. Since H-bonds stabilizing are interchangeable, it is inevitable that form between incorrect pairs amino acids which either incorporated into as defects must be broken before correct can found. This process modeled mapping formation breakage one-dimensional random walk. resulting microscopic model governed two timescales: diffusion...
We computationally examine how adding NaCl to an aqueous solution with α- and γ-glycine nuclei alters the structure interfacial energy of nuclei. The polar nucleus in pure develops a melted layer amorphous glycine around nucleus. When is added, double formed that stabilizes polymorph eliminates surface layer. In contrast, non-polar α-glycine largely unaffected by addition NaCl. To quantify stabilizing effect on nuclei, we alchemically transform into brine glycine. alchemical transformation...