Rationalizing the Formation of Belinostat Solvates with Experimental Screening and Computational Predictions

2021 ◽  
Author(s):  
Zhonghua Li ◽  
Ruiling Ouyang ◽  
Peng Shi ◽  
Shichao Du ◽  
Junbo Gong ◽  
...  
Keyword(s):  
Computational Predictions

scholarly journals Structural insights into the modulation of PDGF/PDGFR-β complexation by hyaluronan derivatives

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Kanagasabai Balamurugan ◽  
Linda Koehler ◽  
Jan-Niklas Dürig ◽  
Ute Hempel ◽  
Jörg Rademann ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cancer Progression ◽  
Computational Analysis ◽  
Vascular Endothelial ◽  
Receptor Recognition ◽  
Dynamics Simulations ◽  
Endothelial Growth Factor ◽  
Structural Insights ◽  
Important Physiological Process ◽  
Computational Predictions

Abstract Angiogenesis is an important physiological process playing a crucial role in wound healing and cancer progression. Vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) are key players in angiogenesis. Based on previous findings regarding the modulation of VEGF activity by glycosaminoglycans (GAG), here we explore the interaction of hyaluronan (HA)-based GAG with PDGF and its receptor PDGFR-β by applying molecular modeling and dynamics simulations in combination with surface plasmon resonance (SPR). Computational analysis on the interaction of oligo-hyaluronan derivatives with different sulfation pattern and functionalization shows that these GAG interact with PDGF in relevant regions for receptor recognition, and that high sulfation as well as modification with the TAMRA group convey stronger binding. On the other hand, the studied oligo-hyaluronan derivatives are predicted to scarcely recognize PDGFR-β. SPR results are in line with the computational predictions regarding the binding pattern of HA tetrasaccharide (HA4) derivatives to PDGF and PDGFR-β. Furthermore, our experimental results also show that the complexation of PDGF to PDGFR-β can be modulated by HA4 derivatives. The results found open the path for considering HA4 derivatives as potential candidates to be exploited for modulation of the PDGF/PDGFR-β signaling system in angiogenesis and related disease conditions.

Computational predictions of metal-macrocycle stability constants require accurate treatments of local solvent and pH effects

2021 ◽  
Author(s):  
Brian Gentry ◽  
Tae Hoon Choi ◽  
William S. Belfield ◽  
John A. Keith
Keyword(s):  
Quantum Chemistry ◽  
Rational Design ◽  
Chelating Agents ◽  
Ph Effects ◽  
Detailed Understanding ◽  
Metal Interactions ◽  
Solvent Phase ◽  
Computational Quantum Chemistry ◽  
Computational Predictions ◽  
Computational Quantum

Rational design of molecular chelating agents requires a detailed understanding of physicochemical ligand-metal interactions in solvent phase. Computational quantum chemistry methods should be able to provide this, but computational reports...

Computational predictions for estimating the maximum deflection of reinforced concrete panels subjected to the blast load

2020 ◽  
Vol 139 ◽  
pp. 103527 ◽  
Author(s):  
Aydin Shishegaran ◽  
Mohammad Reza Khalili ◽  
Behnam Karami ◽  
Timon Rabczuk ◽  
Arshia Shishegaran
Keyword(s):  
Reinforced Concrete ◽  
Blast Load ◽  
Maximum Deflection ◽  
Concrete Panels ◽  
Computational Predictions

Effects of the Main Gas Path Pressure Field on Rim Seal Flows in a Stationary Linear Cascade

2015 ◽  
Author(s):  
Jeffrey Gibson ◽  
Karen Thole ◽  
Jesse Christophel ◽  
Curtis Memory
Keyword(s):  
Bluff Body ◽  
Pressure Field ◽  
Turbine Engines ◽  
Gas Turbine Engines ◽  
Baseline Design ◽  
Linear Cascade ◽  
Blade Row ◽  
High Degree ◽  
Effectiveness Data ◽  
Computational Predictions

Rim seals in the turbine section of gas turbine engines aim to reduce the amount of purge air required to prevent the ingress of hot mainstream gas into the under-platform space. A stationary, linear cascade was designed, built, and benchmarked to study the effect of the interaction between the pressure fields from an upstream vane row and downstream blade row on hot gas ingress for engine-realistic rim seal geometries. The pressure field of the downstream blade row was modeled using a bluff body designed to produce the pressure distortion of a moving blade. Sealing effectiveness data for the baseline seal indicated that there was little to no ingress with a purge rate greater than 1% of the main gas path flow. Adiabatic endwall effectiveness data downstream in the trench between the vane and blade showed a high degree of mixing. Extending the seal feature associated with the vane endwall indicated better sealing than the baseline design. Steady computational predictions were found to overpredict the sealing effectiveness due to underpredicted mixing in the trench.

Computational investigation of the human SOD1 mutant, Cys146Arg, that directs familial amyotrophic lateral sclerosis

2017 ◽  
Vol 13 (8) ◽  
pp. 1495-1503 ◽  
Author(s):  
E. Srinivasan ◽  
R. Rajasekaran
Keyword(s):  
Molecular Dynamics ◽  
Amyotrophic Lateral Sclerosis ◽  
Familial Amyotrophic Lateral Sclerosis ◽  
Computational Investigation ◽  
Conformational Preferences ◽  
Dynamics Simulations ◽  
Sod1 Mutant ◽  
Human Sod1 ◽  
Lateral Sclerosis ◽  
Computational Predictions

Molecular dynamics simulations along with the computational predictions used to assess the protein structural characterization as well as the conformational preferences of the monomeric native and mutant SOD1.

Spreadsheet-Based Computational Predictions of Isotope Effects

2018 ◽  
pp. 403-450
Author(s):  
O. Maduka Ogba ◽  
John D. Thoburn ◽  
Daniel J. O’Leary
Keyword(s):  
Isotope Effects ◽  
Computational Predictions

scholarly journals Computationally assisted design and selection of maneuverable biological walking machines

2020 ◽  
Author(s):  
Jiaojiao Wang ◽  
Junehu Park ◽  
Xiaotian Zhang ◽  
Insu Park ◽  
Evin Kilicarslan ◽  
...  
Keyword(s):  
Robot Design ◽  
Systematic Design ◽  
Forward Motion ◽  
Modeling Simulation ◽  
Walking Machines ◽  
Biological Machines ◽  
Muscle Actuators ◽  
Computational Predictions ◽  
Selection Of ◽  
Dual Ring

ABSTRACTThe intriguing opportunities enabled by the use of living components in biological machines have spurred the development of a variety of muscle-powered bio-hybrid robots in recent years. Among them, several generations of bio-hybrid walkers have been established as reliable platforms to study untethered locomotion. However, despite these advances, such technology is not mature yet, and major challenges remain. This study takes steps to address two of them: the lack of systematic design approaches, common to bio-hybrid robotics in general, and in the case of bio-hybrid walkers specifically, the lack of maneuverability. We then present here a dual-ring biobot, computationally designed and selected to exhibit robust forward motion and rotational steering. This dual-ring biobot consists of two independent muscle actuators and a 4-legged scaffold asymmetric in the fore/aft direction. The integration of multiple muscles within its body architecture, combined with differential electrical stimulation, allows the robot to maneuver. The dual-ring robot design is then fabricated and experimentally tested, confirming computational predictions and turning abilities. Overall, our design approach based on modeling, simulation, and fabrication exemplified in this robot represents a route to efficiently engineer biological machines with adaptive functionalities.

Sign in / Sign up

Export Citation Format

Share Document