Multiple Factors Contribute to the Toxicity of the Aromatic Retinoid, TTNPB (Ro 13-7410): Binding Affinities and Disposition

1997 ◽  
Vol 142 (2) ◽  
pp. 319-327 ◽  
Author(s):  
Michael A. Pignatello ◽  
Frederick C. Kauffman ◽  
Arthur A. Levin
Keyword(s):  
Binding Affinities ◽  
Multiple Factors ◽  
Aromatic Retinoid

scholarly journals Alcohol Binding to the Odorant Binding Protein LUSH: Multiple Factors Affecting Binding Affinities

Biochemistry ◽  
2010 ◽  
Vol 49 (29) ◽  
pp. 6136-6142 ◽  
Author(s):  
Lauren Ader ◽  
David N. M. Jones ◽  
Hai Lin
Keyword(s):  
Binding Protein ◽  
Odorant Binding Protein ◽  
Binding Affinities ◽  
Factors Affecting ◽  
Multiple Factors ◽  
Odorant Binding

Specificity determinants of phosphoprotein phosphatases controlling kinetochore functions

2020 ◽  
Vol 64 (2) ◽  
pp. 325-336 ◽  
Author(s):  
Dimitriya H. Garvanska ◽  
Jakob Nilsson
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Activity Level ◽  
Phosphorylation Sites ◽  
Binding Affinities ◽  
Mitotic Kinases ◽  
Anaphase Onset ◽  
Phosphoprotein Phosphatases ◽  
Linear Motifs ◽  
Temporal And Spatial ◽  
Kinetochore Function

Abstract Kinetochores are instrumental for accurate chromosome segregation by binding to microtubules in order to move chromosomes and by delaying anaphase onset through the spindle assembly checkpoint (SAC). Dynamic phosphorylation of kinetochore components is key to control these activities and is tightly regulated by temporal and spatial recruitment of kinases and phosphoprotein phosphatases (PPPs). Here we focus on PP1, PP2A-B56 and PP2A-B55, three PPPs that are important regulators of mitosis. Despite the fact that these PPPs share a very similar active site, they target unique ser/thr phosphorylation sites to control kinetochore function. Specificity is in part achieved by PPPs binding to short linear motifs (SLiMs) that guide their substrate specificity. SLiMs bind to conserved pockets on PPPs and are degenerate in nature, giving rise to a range of binding affinities. These SLiMs control the assembly of numerous substrate specifying complexes and their position and binding strength allow PPPs to target specific phosphorylation sites. In addition, the activity of PPPs is regulated by mitotic kinases and inhibitors, either directly at the activity level or through affecting PPP–SLiM interactions. Here, we discuss recent progress in understanding the regulation of PPP specificity and activity and how this controls kinetochore biology.

Case Exercise: Biomechanics in Rearend Motor Vehicle Collisions

2007 ◽  
Vol 12 (3) ◽  
pp. 4-7
Author(s):  
Charles N. Brooks ◽  
Christopher R. Brigham
Keyword(s):  
Motor Vehicle ◽  
Body Position ◽  
Motor Vehicle Collisions ◽  
Time Curve ◽  
Vehicle Collisions ◽  
Need For Treatment ◽  
Multiple Factors ◽  
Bodily Injury ◽  
Vehicle Collision ◽  
Physical Findings

Abstract Multiple factors determine the likelihood, type, and severity of bodily injury following a motor vehicle collision and, in turn, influence the need for treatment, extent of disability, and likelihood of permanent impairment. Among the most important factors is the change in velocity due to an impact (Δv). Other factors include the individual's strength and elasticity, body position at the time of impact, awareness of the impending impact (ie, opportunity to brace, guard, or contract muscles before an impact), and effects of braking. Because Δv is the area under the acceleration vs time curve, it combines force and duration and is a useful way to quantify impact severity. The article includes a table showing the results of a literature review that concluded, “the consensus of human subject research conducted to date is that a single exposure to a rear-end impact with a Δv of 5 mph or less is unlikely to result in injury” in most healthy, restrained occupants. Because velocity incorporates direction as well as speed, a vehicular occupant is less likely to be injured in a rear impact than when struck from the side. Evaluators must consider multiple factors, including the occupant's pre-existing physical and psychosocial status, the mechanism and magnitude of the collision, and a variety of biomechanical variables. Recommendations based solely on patient history and physical findings (and, perhaps, imaging studies) may be ill-informed.

Creativity in School: The Synergy of Multiple Factors?

2015 ◽  
Vol 5 (5) ◽  
pp. 445-452
Author(s):  
Carina Alexandra Rondini ◽  
Elizabeth Piemonte Constantino ◽  
Bianca Molica Marinheiro ◽  
Meire Izidoro Santos ◽  
Isabela Torqueti Silva
Keyword(s):  
Multiple Factors

Incidence of depression and its influencing factors in 387 patients with asthma from Xinjiang, China

2020 ◽  
Vol 41 (2) ◽  
pp. e45-e53 ◽  
Author(s):  
Dilinuer Wufuer ◽  
Haidiya Aierken ◽  
Yan Fang ◽  
Mihereguli Simayi ◽  
Kelibiena Tuerxun ◽  
...  
Keyword(s):  
Risk Factors ◽  
Regression Analysis ◽  
Depression Scale ◽  
High Morbidity ◽  
Hamilton Depression Scale ◽  
Multiple Factors ◽  
Asthma Symptoms ◽  
Depression Status ◽  
Treatment Of Depression ◽  
Quality Life

Background: Our study aimed to investigate the incidence of depression in 387 patients with asthma. Methods: The Zung self-rating depression scale and the Hamilton depression scale were used to evaluate the depression status in patients with asthma. Results: Results of logistic regression analysis indicated that, severity of asthma symptoms, taking medicine, frequency of asthma onset, and lack of education were the major risk factors for depression in patients with asthma. Conclusion: Depression is a complication with high morbidity in patients with asthma. It largely affects disease control of asthma and the quality life in patients. Multiple factors are relevant for depression in the patient with asthma. This study provided a comprehensive horizon for clinical management and treatment of depression in patients with asthma.

Automated Assessment of Binding Affinity via Alchemical Free Energy Calculations

2020 ◽  
Author(s):  
Maximilian Kuhn ◽  
Stuart Firth-Clark ◽  
Paolo Tosco ◽  
Antonia S. J. S. Mey ◽  
Mark Mackey ◽  
...  
Keyword(s):  
Free Energy ◽  
Protein Structures ◽  
Free Energy Calculations ◽  
Distinct Advantage ◽  
Binding Affinities ◽  
Structure Based Drug Design ◽  
Energy Calculations ◽  
Kendall’S Τ ◽  
Experimental Values ◽  
Better Than

Free energy calculations have seen increased usage in structure-based drug design. Despite the rising interest, automation of the complex calculations and subsequent analysis of their results are still hampered by the restricted choice of available tools. In this work, an application for automated setup and processing of free energy calculations is presented. Several sanity checks for assessing the reliability of the calculations were implemented, constituting a distinct advantage over existing open-source tools. The underlying workflow is built on top of the software Sire, SOMD, BioSimSpace and OpenMM and uses the AMBER14SB and GAFF2.1 force fields. It was validated on two datasets originally composed by Schrödinger, consisting of 14 protein structures and 220 ligands. Predicted binding affinities were in good agreement with experimental values. For the larger dataset the average correlation coefficient Rp was 0.70 ± 0.05 and average Kendall’s τ was 0.53 ± 0.05 which is broadly comparable to or better than previously reported results using other methods. <br>

SAMPL7 TrimerTrip Host-Guest Binding Poses and Binding Affinities from Spherical-Coordinates-Biased Simulations

2020 ◽  
Author(s):  
Zhaoxi Sun
Keyword(s):  
Free Energy ◽  
Computational Modelling ◽  
Free Energy Calculations ◽  
Energy Estimates ◽  
Binding Affinities ◽  
Spherical Coordinates ◽  
Collective Variables ◽  
Guest Binding ◽  
Starting Point ◽  
Sampl Challenge

Host-guest binding remains a major challenge in modern computational modelling. The newest 7<sup>th</sup> statistical assessment of the modeling of proteins and ligands (SAMPL) challenge contains a new series of host-guest systems. The TrimerTrip host binds to 16 structurally diverse guests. Previously, we have successfully employed the spherical coordinates as the collective variables coupled with the enhanced sampling technique metadynamics to enhance the sampling of the binding/unbinding event, search for possible binding poses and predict the binding affinities in all three host-guest binding cases of the 6<sup>th</sup> SAMPL challenge. In this work, we employed the same protocol to investigate the TrimerTrip host in the SAMPL7 challenge. As no binding pose is provided by the SAMPL7 host, our simulations initiate from randomly selected configurations and are proceeded long enough to obtain converged free energy estimates and search for possible binding poses. The predicted binding affinities are in good agreement with the experimental reference, and the obtained binding poses serve as a nice starting point for end-point or alchemical free energy calculations.

Formation and Trapping of the Thermodynamically Unfavoured Inverted-Hemicucurbit[6]uril

2019 ◽  
Author(s):  
Elena Prigorchenko ◽  
Sandra Kaabel ◽  
Triin Narva ◽  
Anastassia Baškir ◽  
Maria Fomitšenko ◽  
...  
Keyword(s):  
Complex Formation ◽  
Combinatorial Chemistry ◽  
Trifluoroacetic Acid ◽  
Chloride Anion ◽  
Binding Affinities ◽  
Dynamic Covalent Chemistry ◽  
Reaction Selectivity ◽  
Low Concentration ◽  
Dynamic Combinatorial Chemistry ◽  
First Time

Amplification of a thermodynamically unfavoured macrocyclic product through the directed shift of the equilibrium between dynamic covalent chemistry library members is difficult to achieve. We show for the first time that during condensation of formaldehyde and <i>cis</i>-<i>N,N'</i>-cyclohexa-1,2-diylurea formation of <i>inverted-cis</i>-cyclohexanohemicucurbit[6]uril (<i>i-cis</i>-cycHC[6]) can be induced at the expense of thermodynamically favoured <i>cis</i>-cyclohexanohemicucurbit[6]uril (<i>cis</i>-cycHC[6]). The formation of <i>i-cis-</i>cycHC[6] is enhanced in low concentration of the templating chloride anion and suppressed in excess of this template. We found that reaction selectivity is governed by the solution-based template-aided dynamic combinatorial chemistry and continuous removal of the formed cycHC[6] macrocycles from the equilibrating solution by precipitation. Notably, the <i>i-cis</i>-cycHC[6] was isolated with 33% yield. Different binding affinities of three diastereomeric <i>i-cis</i>-, <i>cis</i>-cycHC[6] and their chiral isomer (<i>R,R</i>)-cycHC[6] for trifluoroacetic acid demonstrate the influence of macrocycle geometry on complex formation.

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