Experimental and Computational Modelling of Flow Distribution

AbstractThe primary objective of this research can be divided into two separate aspects. The first one was to verify whether own software can be treated as a viable source of data for the Computer Aided Design (CAD) modelling and Computational Fluid Dynamics CFD analysis. The second aspect was to analyze the influence of the Ventricle Assist Device (VAD) outflow cannula positioning on the blood flow distribution in the brain-supplying arteries. Patient-specific model was reconstructed basing on the DICOM image sets obtained with the angiographic Computed Tomography. The reconstruction process was performed in the custom-created software, whereas the outflow cannulas were added in the SolidWorks software. Volumetric meshes were generated in the Ansys Mesher module. The transient boundary conditions enabled simulating several full cardiac cycles. Performed investigations focused mainly on volume flow rate, shear stress and velocity distribution. It was proven that custom-created software enhances the processes of the anatomical objects reconstruction. Developed geometrical files are compatible with CAD and CFD software – they can be easily manipulated and modified. Concerning the numerical simulations, several cases with varied positioning of the VAD outflow cannula were analyzed. Obtained results revealed that the location of the VAD outflow cannula has a slight impact on the blood flow distribution among the brain supplying arteries.

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

10.26434/chemrxiv.12047103 ◽

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.

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