scholarly journals Coherent Conformational Degrees of Freedom as a Structural Basis for Allosteric Communication

2011 ◽  
Vol 7 (12) ◽  
pp. e1002301 ◽  
Author(s):  
Simon Mitternacht ◽  
Igor N. Berezovsky
Keyword(s):  
Degrees Of Freedom ◽  
Structural Basis ◽  
Allosteric Communication ◽  
Conformational Degrees Of Freedom

scholarly journals Computational High-Throughput Screening of Polymeric Photocatalysts: Exploring the Effect of Composition, Sequence Isomerism and Conformational Degrees of Freedom

2018 ◽  
Author(s):  
isabelle Heath-Apostolopoulos ◽  
Liam Wilbraham ◽  
Martijn Zwijnenburg
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Degrees Of Freedom ◽  
Chemical Space ◽  
Low Cost ◽  
Computational Screening ◽  
Computational Workflow ◽  
Conformational Degrees Of Freedom

We discuss a low-cost computational workflow for the high-throughput screening of polymeric photocatalysts and demonstrate its utility by applying it to a number of challenging problems that would be difficult to tackle otherwise. Specifically we show how having access to a low-cost method allows one to screen a vast chemical space, as well as to probe the effects of conformational degrees of freedom and sequence isomerism. Finally, we discuss both the opportunities of computational screening in the search for polymer photocatalysts, as well as the biggest challenges.

scholarly journals Decoupling of crystalline and conformational degrees of freedom in lipid monolayers

1989 ◽  
Vol 91 (3) ◽  
pp. 1855-1865 ◽  
Author(s):  
John Hjort Ipsen ◽  
Ole G. Mouritsen ◽  
Martin J. Zuckermann
Keyword(s):  
Degrees Of Freedom ◽  
Lipid Monolayers ◽  
Conformational Degrees Of Freedom

scholarly journals Criticality of Lamellar Surfaces by Conformational Degrees of Freedom

1995 ◽  
Vol 5 (9) ◽  
pp. 1161-1178
Author(s):  
B. Bassetti ◽  
G. Mazzoletti ◽  
P. Jona
Keyword(s):  
Degrees Of Freedom ◽  
Conformational Degrees Of Freedom

Evolutionarily Conserved Allosteric Communication in Protein Tyrosine Phosphatases

2018 ◽  
Author(s):  
Michael K. Hjortness ◽  
Laura Riccardi ◽  
Akarawin Hongdusit ◽  
Peter H. Zwart ◽  
Banumathi Sankaran ◽  
...  
Keyword(s):  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Kinetic Studies ◽  
Structural Basis ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine ◽  
Allosteric Communication ◽  
Wide Range ◽  
Evolutionarily Conserved ◽  
Dynamics Simulations

Protein tyrosine phosphatases (PTPs) are an important class of regulatory enzymes that exhibit aberrant activities in a wide range of diseases. A detailed mapping of allosteric communication in these enzymes could, thus, reveal the structural basis of physiologically relevant—and, perhaps, therapeutically informative—perturbations (i.e., mutations, post-translational modifications, or binding events) that influence their catalytic states. This study combines detailed biophysical studies of protein tyrosine phosphatase 1B (PTP1B) with bioinformatic analyses of the PTP family to examine allosteric communication in PTPs. Results of X-ray crystallography, molecular dynamics simulations, and sequence-based statistical analyses indicate that PTP1B possesses a broadly distributed allosteric network that is evolutionarily conserved across the PTP family, and findings from kinetic studies and mutational analyses show that this network is functionally intact in sequence-diverse PTPs. The allosteric network resolved in this study reveals new sites for targeting allosteric inhibitors of PTPs and helps explain the functional influence of a diverse set of disease-associated mutations.

Conformational Entropy as a Means to Control the Behavior of Poly(diketonenamine) Vitrimers In and Out of Equilibrium

2019 ◽  
Author(s):  
Changfei He ◽  
Peter Christensen ◽  
Trevor Seguin ◽  
Brandon Wood ◽  
Kristin Persson ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Glass Transition ◽  
Characteristic Time ◽  
Degrees Of Freedom ◽  
Freezing Temperature ◽  
Thermomechanical Behavior ◽  
Polymer Chains ◽  
Network Density ◽  
Conformational Entropy ◽  
Conformational Degrees Of Freedom

Here we show how to control the thermomechanical behavior of vitrimers, both in and out of equilibrium, by incorporating into the dynamic covalent network linear polymer segments varying in both molecular weight (MW = 0–12 kg mol–1) and conformational degrees of freedom. While increasing MW of linear segments predictably yields a lower storage modulus (E’) at the rubbery plateau after softening above the glass transition (Tg), due to the lower network density, we further find that both Tg and the characteristic time (t*) of stress-relaxation when deformed are independently governed by the conformational entropy of the embodied linear segments. We also find that activation energies (Ea) for vitrimer bond exchange in the solid-state are lower, by as much as 19 kJ mol−1, for networks incorporating flexible chains, and that the network’s topology freezing temperature (Tv) decreases with increasing MW of flexible linear segments, but increases with increasing MW of stiff linear segments. Therefore, the dynamics of vitrimer reconfigurability are influenced not only by the energetics of associative bond exchange for a given network density, but also foundationally by the entropy of polymer chains within the network.

scholarly journals Role of protein dynamics in ion selectivity and allosteric coupling in the NaK channel

2015 ◽  
Vol 112 (50) ◽  
pp. 15366-15371 ◽  
Author(s):  
Joshua B. Brettmann ◽  
Darya Urusova ◽  
Marco Tonelli ◽  
Jonathan R. Silva ◽  
Katherine A. Henzler-Wildman
Keyword(s):  
Ion Selectivity ◽  
Selectivity Filter ◽  
Structural Basis ◽  
Functional Coupling ◽  
Dynamic Coupling ◽  
Allosteric Coupling ◽  
Allosteric Communication ◽  
Dependent Inactivation ◽  
Ion Binding Sites ◽  
Essential Connection

Flux-dependent inactivation that arises from functional coupling between the inner gate and the selectivity filter is widespread in ion channels. The structural basis of this coupling has only been well characterized in KcsA. Here we present NMR data demonstrating structural and dynamic coupling between the selectivity filter and intracellular constriction point in the bacterial nonselective cation channel, NaK. This transmembrane allosteric communication must be structurally different from KcsA because the NaK selectivity filter does not collapse under low-cation conditions. Comparison of NMR spectra of the nonselective NaK and potassium-selective NaK2K indicates that the number of ion binding sites in the selectivity filter shifts the equilibrium distribution of structural states throughout the channel. This finding was unexpected given the nearly identical crystal structure of NaK and NaK2K outside the immediate vicinity of the selectivity filter. Our results highlight the tight structural and dynamic coupling between the selectivity filter and the channel scaffold, which has significant implications for channel function. NaK offers a distinct model to study the physiologically essential connection between ion conduction and channel gating.

Evolutionarily Conserved Allosteric Communication in Protein Tyrosine Phosphatases

2018 ◽  
Author(s):  
Michael K. Hjortness ◽  
Laura Riccardi ◽  
Akarawin Hongdusit ◽  
Peter H. Zwart ◽  
Banumathi Sankaran ◽  
...  
Keyword(s):  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Kinetic Studies ◽  
Structural Basis ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine ◽  
Allosteric Communication ◽  
Wide Range ◽  
Evolutionarily Conserved ◽  
Dynamics Simulations

Protein tyrosine phosphatases (PTPs) are an important class of regulatory enzymes that exhibit aberrant activities in a wide range of diseases. A detailed mapping of allosteric communication in these enzymes could, thus, reveal the structural basis of physiologically relevant—and, perhaps, therapeutically informative—perturbations (i.e., mutations, post-translational modifications, or binding events) that influence their catalytic states. This study combines detailed biophysical studies of protein tyrosine phosphatase 1B (PTP1B) with bioinformatic analyses of the PTP family to examine allosteric communication in PTPs. Results of X-ray crystallography, molecular dynamics simulations, and sequence-based statistical analyses indicate that PTP1B possesses a broadly distributed allosteric network that is evolutionarily conserved across the PTP family, and findings from kinetic studies and mutational analyses show that this network is functionally intact in sequence-diverse PTPs. The allosteric network resolved in this study reveals new sites for targeting allosteric inhibitors of PTPs and helps explain the functional influence of a diverse set of disease-associated mutations.

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