scholarly journals First principles study of the ternary complex model of EL2 defect in GaAs saturable absorber

2012 ◽  
Vol 20 (6) ◽  
pp. 6258 ◽  
Author(s):  
Dechun Li ◽  
Ming Yang ◽  
Yongqing Cai ◽  
Shengzhi Zhao ◽  
Yuanping Feng
Keyword(s):  
Saturable Absorber ◽  
First Principles ◽  
Ternary Complex ◽  
Complex Model ◽  
First Principles Study ◽  
Ternary Complex Model

scholarly journals Investigating allosteric effects on the functional dynamics of β2-adrenergic ternary complexes with enhanced-sampling simulations

2017 ◽  
Vol 8 (5) ◽  
pp. 4019-4026 ◽  
Author(s):  
Noureldin Saleh ◽  
Giorgio Saladino ◽  
Francesco Luigi Gervasio ◽  
Timothy Clark
Keyword(s):  
Ternary Complex ◽  
Cooperative Effect ◽  
Complex Model ◽  
Ternary Complexes ◽  
Enhanced Sampling ◽  
Binding Partner ◽  
Functional Dynamics ◽  
Ternary Complex Model ◽  
Intracellular Binding

We propose an experimentally testable extended ternary complex model, where direction of the cooperative effect between ligand and intracellular binding partner (positive or negative) and its magnitude are predicted to be a characteristic of the ligand signaling bias.

Spare receptors, partial agonists, and ternary complex model of drug action

1987 ◽  
Vol 253 (1) ◽  
pp. E114-E121
Author(s):  
L. D. Homer ◽  
T. B. Nielsen
Keyword(s):  
Ternary Complex ◽  
Drug Action ◽  
Complex Model ◽  
Published Data ◽  
Receptor Ligand ◽  
Spare Receptors ◽  
Contractile Responses ◽  
Partial Agonists ◽  
Receptor Inactivation ◽  
Ternary Complex Model

The occurrence of spare receptors and partial agonists for smooth muscle contractions mediated by alpha 1-adrenergic receptors can be accounted for with a ternary complex model of drug action presented here. In this model, receptor-ligand complexes are assumed to be inactive until the complex binds to an activating protein. Contractile responses are assumed to be proportional to the concentration of ternary complex (receptor-ligand-activator) regardless of the ligand involved. Antagonists are unable to form the ternary complex. Spare receptors are present as the inactive receptor-ligand complex. Such a model is shown to fit already published data on membrane binding of alpha 1-adrenergic agonists as well as contractile responses to the agonist. Schild plots are expected to resemble those of a single-site model of drug action. The double-reciprocal plots of receptor-inactivation studies will display only a slight curvature as may be seen in previously published articles. Partial agonists may have 50% response doses lowe or higher than full agonists. The hypothesis that ternary complexes are formed with alpha 1-receptors could be tested more critically with receptor-inactivation studies using both antagonists and agonists. Partial inactivation of receptor and activator protein should reduce the binding of antagonist without altering the concentration needed to bind to 50% of the receptors. On the other hand, the concentration of agonist required to displace 50% of a bound antagonist is expected to increase. The proposal that contractile responses are proportional to the ternary complex concentration could be tested by fitting the ternary complex model to the data from studies of contractions induced by partial agonists as well as full agonists.

The DRY motif and the four corners of the cubic ternary complex model

2017 ◽  
Vol 35 ◽  
pp. 16-23 ◽  
Author(s):  
G. Enrico Rovati ◽  
Valérie Capra ◽  
Vincent S. Shaw ◽  
Rabia U. Malik ◽  
Sivaraj Sivaramakrishnan ◽  
...  
Keyword(s):  
Ternary Complex ◽  
Complex Model ◽  
Four Corners ◽  
Dry Motif ◽  
Ternary Complex Model

scholarly journals Screening for Positive Allosteric Modulators: Assessment of Modulator Concentration-Response Curves as a Screening Paradigm

2007 ◽  
Vol 12 (5) ◽  
pp. 668-676 ◽  
Author(s):  
Christopher J. Langmead
Keyword(s):  
Ternary Complex ◽  
Screening Method ◽  
Quantitative Relationship ◽  
Complex Model ◽  
Allosteric Modulators ◽  
Response Curves ◽  
Screening Assay ◽  
Positive Modulator ◽  
Ternary Complex Model ◽  
Positive Allosteric Modulators

Targeting allosteric binding sites represents a powerful mechanism for selectively modulating receptor function. The advent of functional assays as the screening method of choice is leading to an increase in the number of allosteric modulators identified. These include positive allosteric modulators that can increase the affinity of the orthosteric agonist and potentiate the evoked response. A common method for screening for positive allosteric modulators is to examine a concentration-response (C/R) curve to the putative modulator in the presence of a single, low concentration of agonist. The study reported here has used data simulations for positive allosteric modulators according to the allosteric ternary complex model to generate modulator C/R curves. The results are then compared to the mechanistic parameters used to simulate the data. It is clear from the simulations that the potency of a positive modulator C/R curve in a screening assay is the product of both its affinity and positive cooperativity. However, it is often difficult to tell which parameter dominates the response; not knowing the actual affinity or cooperativity of a ligand may have consequences for receptor selectivity. Further modeling demonstrates that the use and choice of single agonist concentration, as well as changes in the agonist curve Hill slope, can have significant effects on the modulator C/R curve. Finally, the quantitative relationship between modulator C/R curves and the allosteric ternary complex model is explored. These simulations emphasize the importance of careful interpretation of screening data and of conducting full mechanism of action studies for positive allosteric modulators. ( Journal of Biomolecular Screening 2007:668-676)

First-principles study on the effects of the intrinsic defects in GaAs saturable absorber

2014 ◽  
Author(s):  
Xiaoyang Ma ◽  
Dechun Li ◽  
Shengzhi Zhao ◽  
Wen Cong ◽  
Guiqiu Li ◽  
...  
Keyword(s):  
Saturable Absorber ◽  
First Principles ◽  
Intrinsic Defects ◽  
First Principles Study

scholarly journals Conformational States of Exchange Protein Directly Activated by cAMP (EPAC1) Revealed by Ensemble Modeling and Integrative Structural Biology

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 35 ◽  
Author(s):  
Mark Andrew White ◽  
Tamara Tsalkova ◽  
Fang C. Mei ◽  
Xiaodong Cheng
Keyword(s):  
Bound States ◽  
Ternary Complex ◽  
Complex Model ◽  
Conformational States ◽  
X Ray ◽  
Solution Structures ◽  
X Ray Scattering ◽  
Ternary Complex Model ◽  
Saxs Analysis ◽  
Allosteric Regulators

Exchange proteins directly activated by cAMP (EPAC1 and EPAC2) are important allosteric regulators of cAMP-mediated signal transduction pathways. To understand the molecular mechanism of EPAC activation, we performed detailed Small-Angle X-ray Scattering (SAXS) analysis of EPAC1 in its apo (inactive), cAMP-bound, and effector (Rap1b)-bound states. Our study demonstrates that we can model the solution structures of EPAC1 in each state using ensemble analysis and homology models derived from the crystal structures of EPAC2. The N-terminal domain of EPAC1, which is not conserved between EPAC1 and EPAC2, appears folded and interacts specifically with another component of EPAC1 in each state. The apo-EPAC1 state is a dynamic mixture of a compact (Rg = 32.9 Å, 86%) and a more extended (Rg = 38.5 Å, 13%) conformation. The cAMP-bound form of EPAC1 in the absence of Rap1 forms a dimer in solution; but its molecular structure is still compatible with the active EPAC1 conformation of the ternary complex model with cAMP and Rap1. Herein, we show that SAXS can elucidate the conformational states of EPAC1 activation as it proceeds from the compact, inactive apo conformation through a previously unknown intermediate-state, to the extended cAMP-bound form, and then binds to its effector (Rap1b) in a ternary complex.

scholarly journals First principles study of Bismuth alloying effects in GaAs saturable absorber

2012 ◽  
Vol 20 (10) ◽  
pp. 11574 ◽  
Author(s):  
Dechun Li ◽  
Ming Yang ◽  
Shengzhi Zhao ◽  
Yongqing Cai ◽  
Yuanping Feng
Keyword(s):  
Saturable Absorber ◽  
First Principles ◽  
First Principles Study ◽  
Alloying Effects
Sign in / Sign up

Export Citation Format

Share Document