Evaluation of human obstructive sleep apnea using computational fluid dynamics.

Obstructive sleep apnea (OSA) severity might be correlated to the flow characteristics of the upper airways. We aimed to investigate the severity of OSA based on 3D models constructed from CT scans coupled with computational fluid dynamics (CFD) simulations. The CT scans of seven adult patients diagnosed with OSA were used to reconstruct the 3D models of the upper airways and CFD modeling and analyses were performed. Results from the fluid simulations were compared with the apnea-hypopnea index. Here we show a correlation between a CFD-based parameter, the adjusted pressure coefficient (Cp*), and the respective apnea-hypopnea index (Pearson's r = 0.91, p = 0.004), which suggests that the anatomical-based model coupled with CFD could provide functional and localized information for different regions of the upper airways

Conformational effects on the Circular Dichroism of Human Carbonic Anhydrase II: a multilevel computational study

Circular Dichroism (CD) spectroscopy is a powerful method for investigating conformational changes in proteins and therefore has numerous applications in structural and molecular biology. Here a computational investigation of the CD spectrum of the Human Carbonic Anhydrase II (HCAII), with main focus on the near-UV CD spectra of the wild-type enzyme and it seven tryptophan mutant forms, is presented and compared to experimental studies. Multilevel computational methods (Molecular Dynamics, Semiempirical Quantum Mechanics, Time-Dependent Density Functional Theory) were applied in order to gain insight into the mechanisms of interaction between the aromatic chromophores within the protein environment and understand how the conformational flexibility of the protein influences these mechanisms. The analysis suggests that combining CD semi empirical calculations, crystal structures and molecular dynamics (MD) could help in achieving a better agreement between the computed and experimental protein spectra and provide some unique insight into the dynamic nature of the mechanisms of chromophore interactions

Sand transverse dune aerodynamics: 3D Coherent Flow Structures from a computational study

The engineering interest about dune fields is dictated by the their interaction with a number of human infrastructures in arid environments. Sand dunes dynamics is dictated by wind and its ability to induce sand erosion, transport and deposition. A deep understanding of dune aerodynamics serves then to ground effective strategies for the protection of human infrastructures from sand, the so-called sand mitigation. Because of their simple geometry and their frequent occurrence in desert area, transverse sand dunes are usually adopted in literature as a benchmark to investigate dune aerodynamics by means of both computational or experimental approaches, usually in nominally 2D setups. The present study aims at evaluating 3D flow features in the wake of a idealised transverse dune, if any, under different nominally 2D setup conditions by means of computational simulations and to compare the obtained results with experimental measurements available in literature

An HPC-Based Approach to Study Living System Computational Model Parameter Dependency

High performance computing (HPC) allows one to run in parallel large amount of independent numerical experiments for computationally intensive simulations of a complex system. Results of such experiments can be used to derive dependencies between functional characteristics of simulated system and parameters of the computational model. In this paper, we implemented this HPC approach with using a computational model of the electrical activity in the left ventricle of human heart. To illustrate possibilities of the approach, we analyzed dependencies of electrophysiological characteristics of the left ventricle on the parameters of its geometry. Particularly, we identified a dependence of the dynamics of activated myocardium part during excitation on the model parameters of the myocardial fiber orientation in the ventricular wall

Efficient and Accurate Modeling of Conformational Transitions in Proteins: The Case of c-Src Kinase

The theoretical computational modeling of large conformational transitions occurring in biomolecules still represents a challenge. Here, we present an accurate "in silico" description of the activation and deactivation mechanisms of human c-Src kinases, a fundamental process regulating several crucial cell functions. Our results clearly show that by applying an efficient and automated algorithm able to drive the molecular dynamics (MD) sampling along the pathway between the two c-Src conformational states - the active state and the inactive state - it is possible to accurately describe, at reduced computational costs, the molecular mechanism underlying these large conformational rearrangements. This procedure, combining the MD simulations with the sampling along the well-defined principal motions connecting the two conformational states, allows to provide a description well beyond the present computational limits, and it is easily applicable to different systems where the structures of both the initial and final states are known