scholarly journals Denaturants Alter the Flux through Multiple Pathways in the Folding of PDZ Domain

2017 ◽  
Author(s):  
Zhenxing Liu ◽  
D. Thirumalai
Keyword(s):  
Pdz Domain ◽  
Transfer Model ◽  
Guanidinium Chloride ◽  
Self Organized ◽  
Small Proteins ◽  
Molecular Transfer ◽  
Unfolded State ◽  
The Stability ◽  
Folding Thermodynamics ◽  
Good Agreement

AbstractAlthough we understand many aspects of how small proteins (number of residues less than about hundred) fold, it is a major challenge to understand how large proteins self-assemble. To partially overcome this challenge, we performed simulations using the Self-Organized Polymer model with Side Chains (SOP-SC) in guanidinium chloride (GdmCl), using the Molecular Transfer Model (MTM), to describe the folding of the 110-residue PDZ3 domain. The simulations reproduce the folding thermodynamics accurately including the melting temperature (Tm), the stability of the folded state with respect to the unfolded state. We show that the calculated dependence of ln kobs (kobs is the relaxation rate) has the characteristic Chevron shape. The slopes of the Chevron plots are in good agreement with experiments. We show that PDZ3 folds by four major pathways populating two metastable intermediates, in accord with the kinetic partitioning mechanism. The structure of one of the intermediates, populated after polypeptide chain collapse, is structurally similar to an equilibrium intermediate. Surprisingly, the connectivities between the intermediates and hence, the fluxes through the pathways depend on the concentration of GdmCl. The results are used to predict possible outcomes for unfolding of PDZ domain subject to mechanical forces. Our study demonstrates that, irrespective of the size or topology, simulations based on MTM and SOP-SC offer a framework for describing the folding of proteins, mimicking precisely the conditions used in experiments.

scholarly journals Folding PDZ2 domain using the Molecular Transfer Model

2016 ◽  
Author(s):  
Zhenxing Liu ◽  
Govardhan Reddy ◽  
Dave Thirumalai
Keyword(s):  
Pdz Domain ◽  
High Energy ◽  
Coarse Grained ◽  
Radius Of Gyration ◽  
Transfer Model ◽  
Self Organized ◽  
Energy Profiles ◽  
X Ray Scattering ◽  
Molecular Transfer

A major challenge in molecular simulations is to describe denaturant-dependent folding of proteins order to make direct comparisons within vitroexperiments. We use the molecular transfer model (MTM), which is currently the only method that accomplishes this goal albeit phenomenologically, to quantitatively describe urea-dependent folding of PDZ domain, which plays a significant role in molecular recognition and signaling. Experiments show that urea-dependent unfolding rates of the PDZ2 domain exhibit a downward curvature at high urea concentrations ([C]s), which has been interpreted by invoking the presence of a sparsely populated high energy intermediate. Simulations using the MTM and a coarse-grained Self-Organized Polymer (SOP) representation of PDZ2 are used to show that the intermediate (IEQ), which has some native-like character, is present in equilibrium both in the presence and absence of urea. The free energy profiles as a function of the structural overlap order parameter show that there are two barriers separating the folded and unfolded states. Structures of the transition state ensembles, (TSE1 separating the unfolded and (IEQ) andTSE2 separatingIEQand the native state), determined using thePfoldmethod, show thatTSE1 is greatly expanded whileTSE2 is compact and native-like. Folding trajectories reveal that PDZ2 folds by parallel routes. In one pathway folding occurs exclusively throughI1, which resemblesIEQ. In a fraction of trajectories, constituting the second pathway, folding occurs through a combination ofI1and a kinetic intermediate. We establish that the radius of gyration (RUg) of the unfolded state is more compact (by ∼9%) under native conditions. Theory and simulations show that the decrease inRUgoccurs on the time scale on the order of utmost ∼20μs. The modest decrease inRUgand the rapid collapse suggest that high spatial and temporal resolution, currently beyond the scope of most small angle X-ray scattering experiments, are needed to detect compaction in finite-sized proteins. The present work further establishes that MTM is efficacious in producing nearly quantitative predictions for folding of proteins under conditions used to carry out experiments.

scholarly journals Temperature and Guanidine Hydrochloride effects on the folding thermodynamics of WW domain and variants

2021 ◽  
Author(s):  
Meng Qin ◽  
Zhenxing Liu ◽  
Wei Wang ◽  
D. Thirumalai
Keyword(s):  
Guanidine Hydrochloride ◽  
Transfer Model ◽  
Free Energies ◽  
Ww Domain ◽  
Molecular Transfer ◽  
Go Model ◽  
Β Sheet ◽  
Folding Thermodynamics ◽  
Good Agreement

We use simulations based on an all atom Go model to calculate the folding temperatures (Tfs) and free energies (ΔGs) of two variants of the WW domain, which is a small all β-sheet protein. The results, without adjusting any parameter, are in good agreement with experiments, thus validating the simulations. We then used the Molecular Transfer Model to predict the changes in their ΔG and Tfs as Guanidine Hydrochloride concentration is varied. The predictions can be readily tested in experiments.

A Model for Predicting Temperature of Electrofusion Joints for Polyethylene Pipes

2009 ◽  
Vol 131 (6) ◽  
Author(s):  
Jianfeng Shi ◽  
Jinyang Zheng ◽  
Weican Guo ◽  
Ping Xu ◽  
Yongquan Qin ◽  
...  
Keyword(s):  
Thermal Contact ◽  
Power Input ◽  
Ultrasonic Test ◽  
Thermal Contact Conductance ◽  
Transfer Model ◽  
Contact Conductance ◽  
One Dimensional ◽  
Polyethylene Pipes ◽  
Heating Wire ◽  
Good Agreement

With the increasing application of electrofusion (EF) welding in connecting polyethylene (PE) pipes for gas distribution, more effort has been invested to ensure the safety of the pipeline systems. The objective of this paper is to investigate and understand the temperature distribution during EF welding. A one-dimensional transient heat-transfer model was proposed, taking the variation in the rate of power input, the phase transition of PE, and the thermal contact conductance between heating wire and PE into consideration. Then, experiments were designed to verify the power input and the temperature. The measured values of the power input were shown to be in good agreement with the analytical results. Based on ultrasonic test (UT), a new “Eigen-line” method was presented, which overcomes the difficulties found in the thermocouples’ temperature measurements. The results demonstrate good agreements between prediction and experiment. Finally, based on the presented model, a detailed parametric study was carried out to investigate the influences of the variation in the power input, the physical properties of PE, and the thermal contact conductance between heating wire and surrounding PE.

OPTIMAL VELOCITY MODEL WITH RELATIVE VELOCITY

2006 ◽  
Vol 17 (01) ◽  
pp. 65-73 ◽  
Author(s):  
SHIRO SAWADA
Keyword(s):  
Nonlinear Analysis ◽  
Relative Velocity ◽  
Velocity Model ◽  
Fundamental Diagram ◽  
Optimal Velocity ◽  
Traffic Jam ◽  
Optimal Velocity Model ◽  
Linear And Nonlinear ◽  
The Stability ◽  
Good Agreement

The optimal velocity model which depends not only on the headway but also on the relative velocity is analyzed in detail. We investigate the effect of considering the relative velocity based on the linear and nonlinear analysis of the model. The linear stability analysis shows that the improvement in the stability of the traffic flow is obtained by taking into account the relative velocity. From the nonlinear analysis, the relative velocity dependence of the propagating kink solution for traffic jam is obtained. The relation between the headway and the velocity and the fundamental diagram are examined by numerical simulation. We find that the results by the linear and nonlinear analysis of the model are in good agreement with the numerical results.

scholarly journals High stability of trehalose/maltose binding protein fromThermococcus litoralismakes it a good candidate as a sensitive element in biosensor systems for sugar control

2010 ◽  
Vol 24 (3-4) ◽  
pp. 349-353 ◽  
Author(s):  
Olga I. Povarova ◽  
Olga V. Stepanenko ◽  
Anna I. Sulatskaya ◽  
Irina M. Kuznetsova ◽  
Konstantin K. Turoverov ◽  
...  
Keyword(s):  
Free Energy ◽  
Sensitive Element ◽  
High Stability ◽  
Binding Protein ◽  
Maltose Binding Protein ◽  
Thermococcus Litoralis ◽  
Thermophilic Archaeon ◽  
Unfolded State ◽  
The Stability ◽  
Innate Ability

Fluorescence and circular dichroism in far-UV region were used to study the stability of trehalose/maltose binding protein (TMBP) from hyper thermophilic archaeonThermococcus litoralisand its complex with glucose (TMBP/Glc). The evaluation of difference between free energy of native and unfolded state for TMBP and TMBP/Glc showed that both of them are several times higher than that of proteins from mesophilic organisms. Due to the high stability and innate ability to bind glucose this protein is a good candidate as a sensitive element in biosensor systems for sugar control.

Global Stability Analysis of the Wake behind a Circular Cylinder Based on the POD-Chiba Method

2011 ◽  
Vol 137 ◽  
pp. 72-76
Author(s):  
Wei Zhang ◽  
Xian Wen ◽  
Yan Qun Jiang
Keyword(s):  
Stability Analysis ◽  
Circular Cylinder ◽  
Global Stability ◽  
Dimensional Model ◽  
Global Stability Analysis ◽  
The Stability ◽  
Low Dimensional ◽  
Proper Orthogonal ◽  
Calculated Amount ◽  
Good Agreement

A proper orthogonal decomposition (POD) method is applied to study the global stability analysis for flow past a stationary circular cylinder. The flow database at Re=100 is obtained by CFD software, i.e. FLUENT, with which POD bases are constructed by a snapshot method. Based on the POD bases, a low-dimensional model is established for solving the two-dimensional incompressible NS equations. The stability of the flow solution is evaluated by a POD-Chiba method in the way of the eigensystem analysis for the velocity disturbance. The linear stability analysis shows that the first Hopf bifurcation takes place at Re=46.9, which is in good agreement with available results by other high-order accurate stability analysis methods. However, the calculated amount of POD is little, which shows the availability and advantage of the POD method.

Experimental and Theoretical Investigation of the Supersonic Boundary Layer Stability on the Swept Wing

2008 ◽  
Vol 3 (3) ◽  
pp. 34-38
Author(s):  
Sergey A. Gaponov ◽  
Yuri G. Yermolaev ◽  
Aleksandr D. Kosinov ◽  
Nikolay V. Semionov ◽  
Boris V. Smorodsky
Keyword(s):  
Boundary Layer ◽  
Three Dimensional ◽  
Leading Edge ◽  
Supersonic Boundary Layer ◽  
Mean Flow ◽  
Swept Wing ◽  
Wing Model ◽  
Dimensional Boundary ◽  
The Stability ◽  
Good Agreement

Theoretical and an experimental research results of the disturbances development in a swept wing boundary layer are presented at Mach number М = 2. In experiments development of natural and small amplitude controllable disturbances downstream was studied. Experiments were carried out on a swept wing model with a lenticular profile at a zero attack angle. The swept angle of a leading edge was 40°. Wave parameters of moving disturbances were determined. In frames of the linear theory and an approach of the local self-similar mean flow the stability of a compressible three-dimensional boundary layer is studied. Good agreement of the theory with experimental results for transversal scales of unstable vertices of the secondary flow was obtained. However the calculated amplification rates differ from measured values considerably. This disagreement is explained by the nonlinear processes observed in experiment

Stability and collapse of holes in liquid layers

2018 ◽  
Vol 855 ◽  
pp. 1130-1155 ◽  
Author(s):  
Cunjing Lv ◽  
Michael Eigenbrod ◽  
Steffen Hardt
Keyword(s):  
Liquid Film ◽  
Power Laws ◽  
Theoretical Models ◽  
Liquid Volume ◽  
Capillary Length ◽  
Minimum Thickness ◽  
The Stability ◽  
Film Profile ◽  
Hole Closure ◽  
Good Agreement

We investigate experimentally and theoretically the stability and collapse of holes in liquid layers on bounded substrates with various wettabilities. It is shown that for a liquid layer with a thickness of the order of the capillary length, a stable hole exists when the hole diameter is bigger than a critical value $d_{c}$. Consequently, a further increase of the liquid volume causes the hole to collapse. It is found that$d_{c}$increases with the size of the container, but its dependence on the contact angle is very weak. The experimental results are compared with theory, and good agreement is obtained. Moreover, we present investigations of the dynamics of the hole and the evolution of the liquid film profile after the collapse. The diameter of the hole during collapse and the minimum thickness of the liquid film shortly after the collapse obey different power laws with time. Simple theoretical models are developed which indicate that the collapse of the hole is triggered by surface tension and the subsequent closure process results from inertia, whereas the growth of the liquid column after hole closure results from the balance between the capillary force and inertia. Corresponding scaling coefficients are determined.

Stability of Water-Lubricated, Hydrostatic, Conical Bearings With Spiral Grooves for High-Speed Spindles

2001 ◽  
Vol 124 (2) ◽  
pp. 398-405 ◽  
Author(s):  
S. Yoshimoto ◽  
S. Oshima ◽  
S. Danbara ◽  
T. Shitara
Keyword(s):  
High Speed ◽  
Water Pressure ◽  
Rotating Shaft ◽  
Pressurized Water ◽  
High Speeds ◽  
Theoretical Predictions ◽  
The Stability ◽  
Stability Of Water ◽  
Spiral Grooves ◽  
Good Agreement

In this paper, the stability of water-lubricated, hydrostatic, conical bearings with spiral grooves for high-speed spindles is investigated theoretically and experimentally. In these bearing types, pressurized water is first fed to the inside of the rotating shaft and then introduced into spiral grooves through feeding holes located at one end of each spiral groove. Therefore, water pressure is increased due to the effect of the centrifugal force at the outlets of the feeding holes, which results from shaft rotation. In addition, water pressure is also increased by the viscous pumping effect of the spiral grooves. The stability of the proposed bearing is theoretically predicted using the perturbation method, and calculated results are compared with experimental results. It was consequently found that the proposed bearing is very stable at high speeds and theoretical predictions show good agreement with experimental data.

Heat Transfer in Grinding-Hardening of a Cylindrical Component

2011 ◽  
Vol 325 ◽  
pp. 35-41 ◽  
Author(s):  
Thai Nguyen ◽  
Liang Chi Zhang ◽  
Da Le Sun
Keyword(s):  
Heat Transfer ◽  
Three Dimensional ◽  
Hardened Layer ◽  
Transfer Model ◽  
Plunge Grinding ◽  
Cylindrical Component ◽  
Dimensional Finite Element ◽  
Three Dimensional Finite Element ◽  
Grinding Hardening ◽  
Good Agreement

A three-dimensional finite element heat transfer model incorporating a moving heat source was developed to investigate the heat transfer mechanism in grinding-hardening of a cylindrical component. The model was applied to analyze the grinding-hardening of quenchable steel 1045 by two grinding methods, traverse and plunge grinding. It was found that the heat generated can promote the martensitic phase transformation in the ground workpiece. As a result, a hardened layer with a uniform thickness can be produced by traverse grinding. However, the layer thickness generated by plunge grinding varies circumferentially. The results are in good agreement with the experimental observations.

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