Scholarly Works, Center for Soft Matter and Biological Physics
http://hdl.handle.net/10919/86666
Research articles, presentations, and other scholarshipMon, 17 May 2021 04:52:13 GMT2021-05-17T04:52:13ZProtein Trafficking or Cell Signaling: A Dilemma for the Adaptor Protein TOM1
http://hdl.handle.net/10919/103237
Roach, Tiffany G.; Lang, Helja K. M.; Xiong, Wen; Ryhanen, Samppa J.; Capelluto, Daniel G. S.
Fri, 26 Feb 2021 00:00:00 GMThttp://hdl.handle.net/10919/1032372021-02-26T00:00:00ZLysosomal degradation of ubiquitinated transmembrane protein receptors (cargo) relies on the function of Endosomal Sorting Complex Required for Transport (ESCRT) protein complexes. The ESCRT machinery is comprised of five unique oligomeric complexes with distinct functions. Target of Myb1 (TOM1) is an ESCRT protein involved in the initial steps of endosomal cargo sorting. To exert its function, TOM1 associates with ubiquitin moieties on the cargo via its VHS and GAT domains. Several ESCRT proteins, including TOLLIP, Endofin, and Hrs, have been reported to form a complex with TOM1 at early endosomal membrane surfaces, which may potentiate the role of TOM1 in cargo sorting. More recently, it was found that TOM1 is involved in other physiological processes, including autophagy, immune responses, and neuroinflammation, which crosstalk with its endosomal cargo sorting function. Alteration of TOM1 function has emerged as a phosphoinositide-dependent survival mechanism for bacterial infections and cancer progression. Based on current knowledge of TOM1-dependent cellular processes, this review illustrates how TOM1 functions in coordination with an array of protein partners under physiological and pathological scenarios.Parallel temperature interfaces in the Katz-Lebowitz-Spohn driven lattice gas
http://hdl.handle.net/10919/101815
Mukhamadiarov, Ruslan; Priyanka, Priyanka; Tauber, Uwe C.
Fri, 27 Nov 2020 00:00:00 GMThttp://hdl.handle.net/10919/1018152020-11-27T00:00:00ZWe explore a variant of the Katz–Lebowitz–Spohn (KLS) driven lattice gas in two dimensions, where the lattice is split into two regions that are coupled to heat baths with distinct temperatures. The geometry was arranged such that the temperature boundaries are oriented parallel to the external particle drive and resulting net current. We have explored the changes in the dynamical behavior that are induced by our choice of the hopping rates across the temperature boundaries. If these hopping rates at the interfaces satisfy particle-hole symmetry, the current difference across them generates a vector flow diagram akin to a vortex sheet. We have studied the finite-size scaling of the particle density fluctuations in both temperature regions, and observed that it is controlled by the respective temperature values. Specifically, if the colder subsystem is maintained at the KLS critical temperature, while the hotter subsystem’s temperature is set much higher, the interface current greatly suppresses particle exchange between the two regions. As a result of the ensuing effective subsystem decoupling, strong fluctuations persist in the critical region, whence the particle density fluctuations scale with the KLS critical exponents. However, if both temperatures are set well above the critical temperature, the particle density fluctuations scale according to the totally asymmetric exclusion process (TASEP). In addition, we have measured the entropy production rate in both subsystems; it displays intriguing algebraic decay in the critical region, while it saturates quickly at a small but non-zero level in the hotter region. We have also considered another possible choice of the hopping rates across the temperature interfaces that explicitly breaks particle-hole symmetry. In that case the boundary rates induce a net particle flux across the interfaces that displays power-law behavior, until ultimately the particle exlusion constraints generate a clogging transition to an inert state.Social distancing and epidemic resurgence in agent-based Susceptible-Infectious-Recovered models
http://hdl.handle.net/10919/101508
Mukhamadiarov, Ruslan; Deng, Shengfeng; Serrao, Shannon; Priyanka, Priyanka; Nandi, Riya; Yao, Hong; Tauber, Uwe C.
http://hdl.handle.net/10919/101508Once an epidemic outbreak has been effectively contained through non-pharmaceutical interventions, a safe protocol is required for the subsequent release of social distancing restrictions to prevent a disastrous resurgence of the infection. We report individual-based numerical simulations of stochastic susceptible-infectious-recovered model variants on four distinct spatially organized lattice and network architectures wherein contact and mobility constraints are implemented. We robustly find that the intensity and spatial spread of the epidemic recurrence wave can be limited to a manageable extent provided release of these restrictions is delayed sufficiently (for a duration of at least thrice the time until the peak of the unmitigated outbreak) and long-distance connections are maintained on a low level (limited to less than five percent of the overall connectivity).Parallel Temperature Interfaces in the Katz-Lebowitz-Spohn Driven Lattice Gas
http://hdl.handle.net/10919/100917
Mukhamadiarov, Ruslan I.; Priyanka; Täuber, Uwe C.
http://hdl.handle.net/10919/100917We explore a variant of the Katz-Lebowitz-Spohn (KLS) driven lattice gas in two dimensions, where the lattice is split into two regions that are coupled to heat baths with distinct temperatures. The temperature boundaries are oriented parallel to the external particle drive. If the hopping rates at the interfaces satisfy particle-hole symmetry, the current difference across them generates a vector flow diagram akin to a vortex sheet. We have studied the finite-size scaling of the particle density fluctuations in both temperature regions, and observed that it is controlled by the respective temperature values. If the colder subsystem is maintained at the KLS critical temperature, while the hotter subsystem's temperature is set much higher, the interface current greatly suppresses particle exchange between the two regions. As a result of the ensuing effective subsystem decoupling, strong fluctuations persist in the critical region, whence the particle density fluctuations scale with the KLS critical exponents. However, if both temperatures are set well above the critical temperature, the particle density fluctuations scale according to the totally asymmetric exclusion process (TASEP). We have also measured the entropy production rate in both subsystems; it displays intriguing algebraic decay in the critical region, while it saturates quickly at a small but non-zero level in the hotter region. We have also considered another possible choice of the hopping rates across the temperature interfaces that explicitly breaks particle-hole symmetry. In that case the boundary rates induce a net particle flux across the interfaces that displays power-law behavior, until ultimately the particle exclusion constraints generate a clogging transition to an inert state.Social distancing and epidemic resurgence in agent-based Susceptible-Infectious-Recovered models
http://hdl.handle.net/10919/100916
Mukhamadiarov, Ruslan I.; Deng, Shengfeng; Serrao, Shannon R.; Priyanka; Nandi, Riya; Yao, Louie Hong; Täuber, Uwe C.
http://hdl.handle.net/10919/100916Once an epidemic outbreak has been effectively contained through non-pharmaceutical interventions, a safe protocol is required for the subsequent release of social distancing restrictions to prevent a disastrous resurgence of the infection. We report individual-based numerical simulations of stochastic susceptible-infectious-recovered model variants on four distinct spatially organized lattice and network architectures wherein contact and mobility constraints are implemented. We robustly find that the intensity and spatial spread of the epidemic recurrence wave can be limited to a manageable extent provided release of these restrictions is delayed sufficiently (for a duration of at least thrice the time until the peak of the unmitigated outbreak) and long-distance connections are maintained on a low level (limited to less than five percent of the overall connectivity).Coupled two-species model for the pair contact process with diffusion
http://hdl.handle.net/10919/100915
Deng, S.; Li, W.; Täuber, Uwe C.
Thu, 22 Oct 2020 00:00:00 GMThttp://hdl.handle.net/10919/1009152020-10-22T00:00:00ZThe contact process with diffusion (PCPD) defined by the binary reactions B+B→B+B+B, B+B→∅ and diffusive particle spreading exhibits an unusual active to absorbing phase transition whose universality class has long been disputed. Multiple studies have indicated that an explicit account of particle pair degrees of freedom may be required to properly capture this system's effective long-time, large-scale behavior. We introduce a two-species representation for the PCPD in which single particles B and particle pairs A are dynamically coupled according to the stochastic reaction processes B+B→A, A→A+B, A→∅, and A→B+B, with each particle type diffusing independently. Mean-field analysis reveals that the phase transition of this model is driven by competition and balance between the two species. We employ Monte Carlo simulations in one, two, and three dimensions to demonstrate that this model consistently captures the pertinent features of the PCPD. In the inactive phase, A particles rapidly go extinct, effectively leaving the B species to undergo pure diffusion-limited pair annihilation kinetics B+B→∅. At criticality, both A and B densities decay with the same exponents (within numerical errors) as the corresponding order parameters of the original PCPD, and display mean-field scaling above the upper critical dimension dc=2. In one dimension, the critical exponents for the B species obtained from seed simulations also agree well with previously reported exponent value ranges. We demonstrate that the scaling properties of consecutive particle pairs in the PCPD are identical with that of the A species in the coupled model. This two-species picture resolves the conceptual difficulty for seed simulations in the original PCPD and naturally introduces multiple length scales and timescales to the system, which are also the origin of strong corrections to scaling. The extracted moment ratios from our simulations indicate that our model displays the same temporal crossover behavior as the PCPD, which further corroborates its full dynamical equivalence with our coupled model.Critical dynamics of anisotropic antiferromagnets in an external field
http://hdl.handle.net/10919/100914
Nandi, Riya; Täuber, Uwe C.
Tue, 03 Mar 2020 00:00:00 GMThttp://hdl.handle.net/10919/1009142020-03-03T00:00:00ZWe numerically investigate the non-equilibrium critical dynamics in three-dimensional anisotropic antiferromagnets in the presence of an external magnetic field. The phase diagram of this system exhibits two critical lines that meet at a bicritical point. The non-conserved components of the staggered magnetization order parameter couple dynamically to the conserved component of the magnetization density along the direction of the external field. Employing a hybrid computational algorithm that combines reversible spin precession with relaxational Monte Carlo updates, we study the aging scaling dynamics for the model C critical line, identifying the critical initial slip, autocorrelation, and aging exponents for both the order parameter and conserved field, thus also verifying the dynamic critical exponent. We further probe the model F critical line by investigating the system size dependence of the characteristic spin wave frequencies near criticality, and measure the dynamic critical exponents for the order parameter including its aging scaling at the bicritical point.Structural, in silico, and functional analysis of a Disabled-2-derived peptide for recognition of sulfatides
http://hdl.handle.net/10919/100300
Song, Wei; Gottschalk, Carter J.; Tang, Tuo-Xian; Biscardi, Andrew; Ellena, Jeffrey F.; Finkielstein, Carla V.; Brown, Anne M.; Capelluto, Daniel G. S.
Tue, 11 Aug 2020 00:00:00 GMThttp://hdl.handle.net/10919/1003002020-08-11T00:00:00ZDisabled-2 (Dab2) is an adaptor protein that regulates the extent of platelet aggregation by two mechanisms. In the first mechanism, Dab2 intracellularly downregulates the integrin alpha (IIb)beta (3) receptor, converting it to a low affinity state for adhesion and aggregation processes. In the second mechanism, Dab2 is released extracellularly and interacts with the pro-aggregatory mediators, the integrin alpha (IIb)beta (3) receptor and sulfatides, blocking their association to fibrinogen and P-selectin, respectively. Our previous research indicated that a 35-amino acid region within Dab2, which we refer to as the sulfatide-binding peptide (SBP), contains two potential sulfatide-binding motifs represented by two consecutive polybasic regions. Using molecular docking, nuclear magnetic resonance, lipid-binding assays, and surface plasmon resonance, this work identifies the critical Dab2 residues within SBP that are responsible for sulfatide binding. Molecular docking suggested that a hydrophilic region, primarily mediated by R42, is responsible for interaction with the sulfatide headgroup, whereas the C-terminal polybasic region contributes to interactions with acyl chains. Furthermore, we demonstrated that, in Dab2 SBP, R42 significantly contributes to the inhibition of platelet P-selectin surface expression. The Dab2 SBP residues that interact with sulfatides resemble those described for sphingolipid-binding in other proteins, suggesting that sulfatide-binding proteins share common binding mechanisms.Exploring optimization strategies for improving explicit water models: Rigid n-point model and polarizable model based on Drude oscillator
http://hdl.handle.net/10919/99588
Xiong, Yeyue; Onufriev, Alexey V.
Thu, 14 Nov 2019 00:00:00 GMThttp://hdl.handle.net/10919/995882019-11-14T00:00:00ZRigid n-point water models are widely used in atomistic simulations, but have known accuracy drawbacks. Increasing the number of point charges, as well as adding electronic polarizability, are two common strategies for accuracy improvements. Both strategies come at considerable computational cost, which weighs heavily against modest possible accuracy improvements in practical simulations. In an effort to provide guidance for model development, here we have explored the limiting accuracy of “electrostatically globally optimal” npoint water models in terms of their ability to reproduce properties of water dimer—a mimic of the condensed state of water. For a given n, each model is built upon a set of reference multipole moments (e.g. ab initio) and then optimized to reproduce water dimer total dipole moment. The models are then evaluated with respect to the accuracy of reproducing the geometry of the water dimer. We find that global optimization of the charge distribution alone can deliver high accuracy of the water model: for n = 4 or n = 5, the geometry of the resulting water dimer can be almost within 50 of the ab initio reference, which is half that of the experimental error margin. Thus, global optimization of the charge distribution of classical n-point water models can lead to high accuracy models. We also find that while the accuracy improvement in going from n = 3 to n = 4 is substantial, the additional accuracy increase in going from n = 4 to n = 5 is marginal. Next, we have explored accuracy limitations of the standard practice of adding electronic polarizability (via a Drude particle) to a “rigid base”—pre-optimization rigid n-point water model. The resulting model (n = 3) shows a relatively small improvement in accuracy, suggesting that the strategy of merely adding the polarizability to an inferior accuracy water model used as the base cannot fix the defects of the latter. An alternative strategy in which the parameters of the rigid base model are globally optimized along with the polarizability parameter is much more promising: the resulting 3-point polarizable model out-performs even the 5-point optimal rigid model by a large margin. We suggest that future development efforts consider 3- and 4-point polarizable models where global optimization of the “rigid base” is coupled to optimization of the polarizability to deliver globally optimal solutions.Strongly Bent Double-Stranded DNA: Reconciling Theory and Experiment
http://hdl.handle.net/10919/96716
Drozdetski, Aleksander V.; Mukhopadhyay, Abhishek; Onufriev, Alexey V.
Fri, 29 Nov 2019 00:00:00 GMThttp://hdl.handle.net/10919/967162019-11-29T00:00:00ZThe strong bending of polymers is poorly understood. We propose a general quantitative framework of polymer bending that includes both the weak and strong bending regimes on the same footing, based on a single general physical principle. As the bending deformation increases beyond a certain (polymer-specific) point, the change in the convexity properties of the effective bending energy of the polymer makes the harmonic deformation energetically unfavorable: in this strong bending regime the energy of the polymer varies linearly with the average bending angle as the system follows the convex hull of the deformation energy function. For double-stranded DNA, the effective bending deformation energy becomes non-convex for bends greater than similar to 2 degrees per base-pair, equivalent to the curvature of a closed circular loop of similar to 160 base pairs. A simple equation is derived for the polymer loop energy that covers both the weak and strong bending regimes. The theory shows quantitative agreement with recent DNA cyclization experiments on short DNA fragments, while maintaining the expected agreement with experiment in the weak bending regime. Counter-intuitively, cyclization probability (j-factor) of very short DNA loops is predicted to increase with decreasing loop length; the j-factor reaches its minimum for loops of similar or equal to 45 base pairs. Atomistic simulations reveal that the attractive component of the short-range Lennard-Jones interaction between the backbone atoms can explain the underlying non-convexity of the DNA effective bending energy, leading to the linear bending regime. Applicability of the theory to protein-DNA complexes, including the nucleosome, is discussed.