Browsing by Author "Lu, Wei"
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Item A structural dynamics model for how CPEB3 binding to SUMO2 can regulate translational control in dendritic spines(Public Library of Science, 2022) Gu, Xinyu; Schafer, Nicholas P.; Bueno, Carlos; Lu, Wei; Wolynes, Peter G.; Center for Theoretical Biological PhysicsA prion-like RNA-binding protein, CPEB3, can regulate local translation in dendritic spines. CPEB3 monomers repress translation, whereas CPEB3 aggregates activate translation of its target mRNAs. However, the CPEB3 aggregates, as long-lasting prions, may raise the problem of unregulated translational activation. Here, we propose a computational model of the complex structure between CPEB3 RNA-binding domain (CPEB3-RBD) and small ubiquitin-like modifier protein 2 (SUMO2). Free energy calculations suggest that the allosteric effect of CPEB3-RBD/SUMO2 interaction can amplify the RNA-binding affinity of CPEB3. Combining with previous experimental observations on the SUMOylation mode of CPEB3, this model suggests an equilibrium shift of mRNA from binding to deSUMOylated CPEB3 aggregates to binding to SUMOylated CPEB3 monomers in basal synapses. This work shows how a burst of local translation in synapses can be silenced following a stimulation pulse, and explores the CPEB3/SUMO2 interplay underlying the structural change of synapses and the formation of long-term memories.Item Coarse-Grained Modeling and Molecular Dynamics Simulations of Ca2+-Calmodulin(Frontiers, 2021) Nde, Jules; Zhang, Pengzhi; Ezerski, Jacob C.; Lu, Wei; Knapp, Kaitlin; Wolynes, Peter G.; Cheung, Margaret S.; Center for Theoretical Biological PhysicsCalmodulin (CaM) is a calcium-binding protein that transduces signals to downstream proteins through target binding upon calcium binding in a time-dependent manner. Understanding the target binding process that tunes CaM’s affinity for the calcium ions (Ca2+), or vice versa, may provide insight into how Ca2+-CaM selects its target binding proteins. However, modeling of Ca2+-CaM in molecular simulations is challenging because of the gross structural changes in its central linker regions while the two lobes are relatively rigid due to tight binding of the Ca2+ to the calcium-binding loops where the loop forms a pentagonal bipyramidal coordination geometry with Ca2+. This feature that underlies the reciprocal relation between Ca2+ binding and target binding of CaM, however, has yet to be considered in the structural modeling. Here, we presented a coarse-grained model based on the Associative memory, Water mediated, Structure, and Energy Model (AWSEM) protein force field, to investigate the salient features of CaM. Particularly, we optimized the force field of CaM and that of Ca2+ ions by using its coordination chemistry in the calcium-binding loops to match with experimental observations. We presented a “community model” of CaM that is capable of sampling various conformations of CaM, incorporating various calcium-binding states, and carrying the memory of binding with various targets, which sets the foundation of the reciprocal relation of target binding and Ca2+ binding in future studies.Item Computationally exploring the mechanism of bacteriophage T7 gp4 helicase translocating along ssDNA(National Academy of Sciences, 2022) Jin, Shikai; Bueno, Carlos; Lu, Wei; Wang, Qian; Chen, Mingchen; Chen, Xun; Wolynes, Peter G.; Gao, Yang; Center for Theoretical Biological PhysicsBacteriophage T7 gp4 helicase has served as a model system for understanding mechanisms of hexameric replicative helicase translocation. The mechanistic basis of how nucleoside 5′-triphosphate hydrolysis and translocation of gp4 helicase are coupled is not fully resolved. Here, we used a thermodynamically benchmarked coarse-grained protein force field, Associative memory, Water mediated, Structure and Energy Model (AWSEM), with the single-stranded DNA (ssDNA) force field 3SPN.2C to investigate gp4 translocation. We found that the adenosine 5′-triphosphate (ATP) at the subunit interface stabilizes the subunit–subunit interaction and inhibits subunit translocation. Hydrolysis of ATP to adenosine 5′-diphosphate enables the translocation of one subunit, and new ATP binding at the new subunit interface finalizes the subunit translocation. The LoopD2 and the N-terminal primase domain provide transient protein–protein and protein–DNA interactions that facilitate the large-scale subunit movement. The simulations of gp4 helicase both validate our coarse-grained protein–ssDNA force field and elucidate the molecular basis of replicative helicase translocation.Item Detecting the Biopolymer Behavior of Graphene Nanoribbons in Aqueous Solution(Springer Nature, 2016) Wijeratne, Sithara S.; Penev, Evgeni S.; Lu, Wei; Li, Jingqiang; Duque, Amanda L.; Yakobson, Boris I.; Tour, James M.; Kiang, Ching-Hwa; Chemistry; Bioengineering; Materials Science and Nanoengineering; Physics and Astronomy; Smalley-Curl InstituteGraphene nanoribbons (GNR), can be prepared in bulk quantities for large-area applications by reducing the product from the lengthwise oxidative unzipping of multiwalled carbon nanotubes (MWNT). Recently, the biomaterials application of GNR has been explored, for example, in the pore to be used for DNA sequencing. Therefore, understanding the polymer behavior of GNR in solution is essential in predicting GNR interaction with biomaterials. Here, we report experimental studies of the solution-based mechanical properties of GNR and their parent products, graphene oxide nanoribbons (GONR). We used atomic force microscopy (AFM) to study their mechanical properties in solution and showed that GNR and GONR have similar force-extension behavior as in biopolymers such as proteins and DNA. The rigidity increases with reducing chemical functionalities. The similarities in rigidity and tunability between nanoribbons and biomolecules might enable the design and fabrication of GNR-biomimetic interfaces.Item Dynamic response of exchange bias in graphene nanoribbons(American Institute of Physics, 2012) Jammalamadaka, S. Narayana; Rao, S.S.; Vanacken, J.; Moshchalkov, V.V.; Lu, Wei; Tour, J.M.; Smalley Institute for Nanoscale Science and TechnologyThe dynamics of magnetic hysteresis, including the training effect and the field sweep rate dependence of the exchange bias, is experimentally investigated in exchange-coupled potassium split graphenenanoribbons (GNRs). We find that, at low field sweep rate, the pronounced absolute training effect is present over a large number of cycles. This is reflected in a gradual decrease of the exchange bias with the sequential field cycling. However, at high field sweep rate above 0.5 T/min, the training effect is not prominent. With the increase in field sweep rate, the average value of exchange bias field grows and is found to follow power-law behavior. The response of the exchange bias field to the field sweep rate variation is linked to the difference in the time it takes to perform a hysteresis loop measurement compared with the relaxation time of the anti-ferromagnetically aligned spins. The present results may broaden our current understanding of magnetism of GNRs and would be helpful in establishing the GNRs-based spintronic devices.Item Electrical transport in a single-electron transistor coupled to a tunable environment(1999) Lu, Wei; Rimberg, Alexander J.A novel model system is developed to study the effects of the environment on transport properties of a superconducting single-electron transistor (S-SET). The impedance of a two-dimensional electron gas (2DEG) 50 nm below the sample surface serving as the environment can be tuned in situ. A quantum dot is readily formed in the 2DEG. Josephson tunneling processes in the SET are suppressed and quasiparticle tunneling processes are enhanced as the 2DEG is confined. Important energetic parameters of the SET such as the charging energy $E\sb{c}$ and superconducting energy gap $\triangle$ remain almost unchanged in this process.Item Energy landscape underlying spontaneous insertion and folding of an alpha-helical transmembrane protein into a bilayer(Springer Nature, 2018) Lu, Wei; Schafer, Nicholas P.; Wolynes, Peter G.Membrane protein folding mechanisms and rates are notoriously hard to determine. A recent force spectroscopy study of the folding of an α-helical membrane protein, GlpG, showed that the folded state has a very high kinetic stability and a relatively low thermodynamic stability. Here, we simulate the spontaneous insertion and folding of GlpG into a bilayer. An energy landscape analysis of the simulations suggests that GlpG folds via sequential insertion of helical hairpins. The rate-limiting step involves simultaneous insertion and folding of the final helical hairpin. The striking features of GlpG's experimentally measured landscape can therefore be explained by a partially inserted metastable state, which leads us to a reinterpretation of the rates measured by force spectroscopy. Our results are consistent with the helical hairpin hypothesis but call into question the two-stage model of membrane protein folding as a general description of folding mechanisms in the presence of bilayers.Item Nanocomposite oil sensors for downhole hydrocarbon detection(2016-06-28) Tour, James M.; Hwang, Chih-chau; Lu, Wei; Ruan, Gedeng; Tomson, Mason B.; Kan, Amy; Wang, Lu; Wong, Michael S.; Kini, Gautam; Hirasaki, George J.; Miller, Clarence; Rice University; United States Patent and Trademark OfficeVarious embodiments of the present disclosure pertain to nanocomposites for detecting hydrocarbons in a geological structure. In some embodiments, the nanocomposites include: a core particle; a polymer associated with the core particle; a sulfur-based moiety associated with the polymer; and a releasable probe molecule associated with the core particle, where the releasable probe molecule is releasable from the core particle upon exposure to hydrocarbons. Additional embodiments of the present disclosure pertain to methods of detecting hydrocarbons in a geological structure by utilizing the nanocomposites of the present disclosure.Item OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations(Public Library of Science, 2021) Lu, Wei; Bueno, Carlos; Schafer, Nicholas P.; Moller, Joshua; Jin, Shikai; Chen, Xun; Chen, Mingchen; Gu, Xinyu; Davtyan, Aram; Pablo, Juan J. de; Wolynes, Peter G.; Center for Theoretical Biological PhysicsWe present OpenAWSEM and Open3SPN2, new cross-compatible implementations of coarse-grained models for protein (AWSEM) and DNA (3SPN2) molecular dynamics simulations within the OpenMM framework. These new implementations retain the chemical accuracy and intrinsic efficiency of the original models while adding GPU acceleration and the ease of forcefield modification provided by OpenMM’s Custom Forces software framework. By utilizing GPUs, we achieve around a 30-fold speedup in protein and protein-DNA simulations over the existing LAMMPS-based implementations running on a single CPU core. We showcase the benefits of OpenMM’s Custom Forces framework by devising and implementing two new potentials that allow us to address important aspects of protein folding and structure prediction and by testing the ability of the combined OpenAWSEM and Open3SPN2 to model protein-DNA binding. The first potential is used to describe the changes in effective interactions that occur as a protein becomes partially buried in a membrane. We also introduced an interaction to describe proteins with multiple disulfide bonds. Using simple pairwise disulfide bonding terms results in unphysical clustering of cysteine residues, posing a problem when simulating the folding of proteins with many cysteines. We now can computationally reproduce Anfinsen’s early Nobel prize winning experiments by using OpenMM’s Custom Forces framework to introduce a multi-body disulfide bonding term that prevents unphysical clustering. Our protein-DNA simulations show that the binding landscape is funneled towards structures that are quite similar to those found using experiments. In summary, this paper provides a simulation tool for the molecular biophysics community that is both easy to use and sufficiently efficient to simulate large proteins and large protein-DNA systems that are central to many cellular processes. These codes should facilitate the interplay between molecular simulations and cellular studies, which have been hampered by the large mismatch between the time and length scales accessible to molecular simulations and those relevant to cell biology.Item Single-electron transistor: Effects of the environment and detecting electron motion in real time(2003) Lu, Wei; Rimberg, Alexander J.This thesis will be divided into two parts. In the first part, theory and results of a novel system in which a superconducting single-electron transistor (S-SET) coupled to a two-dimensional electron gas (2DEG) serving as a tunable electromagnetic environment for the S-SET will be discussed, including effects of dissipation, resonant tunneling with photon emission, and photon-assisted tunneling. In the second part, we discuss the techniques for which the SET is incorporated in an RF resonant circuit, resulting in an ultra high charge sensitivity and bandwidth. After the 2DEG is confined into a quantum dot, random telegraph signals (RTS) caused by individual electrons tunneling on and off the dot have been observed. In the equilibrium configuration, the occupational probabilities of the charge states of the dot can be directly measured from the RTS and were found to follow a Fermi distribution. In the non-equilibrium configuration, the RTS correctly detected the onset of the current through the dot.Item Single-molecule conformational dynamics of a transcription factor reveals a continuum of binding modes controlling association and dissociation(Oxford University Press, 2021) Chen, Wei; Lu, Wei; Wolynes, Peter G; Komives, Elizabeth A; Center for Theoretical Biological PhysicsBinding and unbinding of transcription factors to DNA are kinetically controlled to regulate the transcriptional outcome. Control of the release of the transcription factor NF-κB from DNA is achieved through accelerated dissociation by the inhibitor protein IκBα. Using single-molecule FRET, we observed a continuum of conformations of NF-κB in free and DNA-bound states interconverting on the subseconds to minutes timescale, comparable to in vivo binding on the seconds timescale, suggesting that structural dynamics directly control binding kinetics. Much of the DNA-bound NF-κB is partially bound, allowing IκBα invasion to facilitate DNA dissociation. IκBα induces a locked conformation where the DNA-binding domains of NF-κB are too far apart to bind DNA, whereas a loss-of-function IκBα mutant retains the NF-κB conformational ensemble. Overall, our results suggest a novel mechanism with a continuum of binding modes for controlling association and dissociation of transcription factors.Item Solvent-based methods for production of graphene nanoribbons(2016-11-15) Tour, James M.; Lu, Wei; Genorio, Bostjan; Rice University; United States Patent and Trademark OfficeThe present invention provides methods of preparing functionalized graphene nanoribbons. Such methods include: (1) exposing a plurality of carbon nanotubes (CNTs) to an alkali metal source in the presence of an aprotic solvent to open them; and (2) exposing the opened CNTs to an electrophile to form functionalized graphene nanoribbons (GNRs). The methods may also include a step of exposing the opened CNTs to a protic solvent to quench any reactive species on them. Additional methods include preparing unfunctionalized GNRs by: (1) exposing a plurality of CNTs to an alkali metal source in the presence of an aprotic solvent to open them; and (2) exposing the opened CNTs to a protic solvent to form unfunctionalized GNRs.Item Synthesis of Carbon Nanomaterials and Their Applications in the Oilfield(2013-09-16) Lu, Wei; Tour, James M.; Billups, W. Edward; Wong, Michael S.This dissertation explores the potential applications of nanotechnology in the oilfield including poly(vinyl alcohol) stabilized carbon black nanoparticles for oil exploration and temperature-responsive carbon black nanoparticles for enhanced oil recovery. Also, it describes the rational design of graphene nanoribbons via intercalating reactive metals into multi-walled carbon nanotubes followed by addition of vinyl monomers or haloalkanes. Efficient production and modification of these aforementioned nanomaterials will make them more attractive for applications in the oilfield and electronics materials. A method is reported for detecting the hydrocarbon in the porous media with stabilized nanoparticles that are capable of efficiently transporting hydrophobic molecules through oil-containing rocks and selectively releasing them when a hydrocarbon is encountered. Nano-sized carbon black was oxidized and then functionalized with poly(vinyl alcohol) via a coupling reaction between the polymer's hydroxyl groups and the carboxylic groups on oxidized carbon black. Breakthrough curves show that poly(vinyl alcohol)-coated oxidized carbon black was stable in synthetic sea brine at room temperature and could carry the 14C-labeled radioactive tracer 2,2ˊ,5,5ˊ-tetrachlorobiphenyl through rocks and then released the tracer upon exposure to hydrocarbon. Due to the temperature-sensitivity of hydrogen bonds, higher molecular weight poly(vinyl alcohol) was used to improve the stability of carbon black nanoparticles in synthetic sea brine at higher temperatures. After sulfation, high molecular weight poly(vinyl alcohol) could stabilized carbon black nanoparticles in American Petroleum Institute standard brine at high temperatures. Those nanoparticles could efficiently transport mass-tagged probe molecules through a variety of oil-field rock types and selectively released the probe molecules into the hydrocarbon-containing rocks. Those proof-of-concept chemical nanoreporters can potentially be used under conditions commonly observed in the reservoir, and aid in the recovery of oil that remains in place. Amphiphilic carbon nanoparticles have been prepared that are capable of reversibly transferring across the water/oil interface in a temperature-controlled manner. Nano-sized carbon black was oxidized and then functionalized with amphiphilic diblock polyethylene-b-poly(ethylene glycol) copolymers that were water-soluble at low-to-moderate temperatures but oil-soluble at higher temperatures. The correlation between the phase transfer temperature and the melting temperature of the hydrophobic block of the copolymers and the weight percent of hydrophilic block were investigated. The amphiphilic nanoparticles were used to stabilize oil droplets for demonstrating potential applications in reducing the water/oil interfacial tension, a key parameter in optimizing crude oil extraction from downhole reservoirs. Graphene nanoribbons free of oxidized surfaces can be prepared in large batches and 100% yield by splitting multi-walled carbon nanotubes with potassium vapor. If desired, exfoliation is attainable in a subsequent step using chlorosulfonic acid. The low-defect density of these GNRs is indicated by their electrical conductivity, comparable to that of graphene derived from mechanically exfoliated graphite. Additionally, cost-effective and potentially industrially scalable, in situ functionalization procedures for preparation of soluble graphene nanoribbons from commercially carbon nanotubes are presented. To make alkane-functionalized graphene nanoribbons, multi-walled carbon nanotubes were intercalated by sodium/potassium alloy under liquid-phase conditions, followed by addition of haloalkanes, while polymer-functionalized graphene nanoribbons were prepared via polymerizing vinyl monomers using potassium-intercalated graphene nanoribbons. The correlation between the splitting of MWCNTs, the intrinsic properties of the intercalants and the degree of graphitization of the starting MWCNTs has also been demonstrated. Those functionalized graphene nanoribbons could have applications in conductive composites, transparent electrodes, transparent heat circuits, and supercapcitors.Item Synthesis of magnetic carbon nanoribbons and magnetic functionalized carbon nanoribbons(2016-09-20) Tour, James M.; Genorio, Bostjan; Lu, Wei; Price-hoelscher, Brandi Katherine; Rice University; M-I, L.L.C.; United States Patent and Trademark OfficeVarious embodiments of the present disclosure pertain to methods of making magnetic carbon nanoribbons. Such methods generally include: (1) forming carbon nanoribbons by splitting carbon nanomaterials; and (2) associating graphene nanoribbons with magnetic materials, precursors of magnetic materials, or combinations thereof. Further embodiments of the present disclosure also include a step of reducing the precursors of magnetic materials to magnetic materials. In various embodiments, the associating occurs before, during or after the splitting of the carbon nanomaterials. In some embodiments, the methods of the present disclosure further comprise a step of (3) functionalizing the carbon nanoribbons with functionalizing agents. In more specific embodiments, the functionalizing occurs in situ during the splitting of carbon nanomaterials. In further embodiments, the carbon nanoribbons are edge-functionalized. Additional embodiments of the present disclosure pertain to magnetic carbon nanoribbon compositions that were formed in accordance with the methods of the present disclosure.Item Understanding the folding mechanisms of membrane proteins through molecular simulations and energy landscape analysis(2021-04-12) Lu, Wei; Wolynes, Peter G.The folding mechanisms of membrane proteins are notoriously hard to determine, due to the multiple events involved in the folding process. In recent years, the development of single molecule techniques has opened the door to studying individual folding events experimentally. However, even in these single molecule experiments the structural details underlying the observed transitions can only be inferred. Similar to E. coli as a model organism, rhomboid protease GlpG is typically used to study membrane protein. Previous single molecular experiments have suggested that GlpG has an anomalously low thermodynamic stability. By performing molecular simulations and energy landscape analysis, we showed that the seemingly low stability was due to the presence of folding intermediates. Our finding was confirmed by a subsequent experimental study by the same experimental group, where our predicted intermediates were observed. On the technique side, we developed our next generation simulation package: OpenAWSEM and Open3SPN2. OpenAWSEM achieves orders of magnitude of speedup with GPU compared with single core CPU, and enables rapid prototyping force fields with automatic derivative calculations.Item Wellbore fluids incorporating magnetic carbon nanoribbons and magnetic functionalized carbon nanoribbons and methods of using the same(2019-01-15) Tour, James M.; Genorio, Bostjan; Lu, Wei; Hoelscher, Katherine Price; Friedheim, James; Patel, Arvind D.; Rice University; United States Patent and Trademark OfficeA wellbore fluid may include an oleaginous continuous phase, one or more magnetic carbon nanoribbons, and at least one weighting agent. A method of performing wellbore operations may include circulating a wellbore fluid comprising a magnetic carbon nanoribbon composition and a base fluid through a wellbore. A method for electrical logging of a subterranean well may include placing into the subterranean well a logging medium, wherein the logging medium comprises a non-aqueous fluid and one or more magnetic carbon nanoribbons, wherein the one or more magnetic carbon nanoribbons are present in a concentration so as to permit the electrical logging of the subterranean well; and acquiring an electrical log of the subterranean well.