355 - Supercomputing for COVID-19

Guests: Andrew Emerson (hpc.cineca.it/staff/emerson-andrew), Daniel Jacobson (ornl.gov/staff-profile/daniel-jacobson)

Host: Markus Voelter Shownoter: Andy Joiner

In this episode we look at how supercomputers are used to help with managing the pandemic. It’s a double-header with two guests. We start with Cineca (cineca.it/en)‘s Andrew Emerson (hpc.cineca.it/staff/emerson-andrew). As part of the EXSCALATE 4 COV (exscalate4cov.eu) EU-funded research project, he works of virtual screening of existing drugs regarding their potential efficacy against SARS-CoV-2. In part two we talk with Dan Jacobson (ornl.gov/staff-profile/daniel-jacobson) of the Oak Ridge National Laboratory (ornl.gov). He and his team used a big data analysis to understand how the virus “works”, and they figured out very interesting mechanisms and pathways.

Introduction
00:03:14
Andrew Emerson (twitter.com/andrewpjemerson?lang=en) | Cineca Supercomputer Center (en.wikipedia.org/wiki/CINECA) | Exscalate4Cov Project (exscalate4cov.eu) | Computer Aided Drug Design (en.wikipedia.org/wiki/Drug_design#Computer-aid…) | Simulation (en.wikipedia.org/wiki/Computer_simulation) | Modelling (en.wikipedia.org/wiki/Computational_model) | Synthesize (en.wikipedia.org/wiki/Chemical_synthesis) | Side Effects (en.wikipedia.org/wiki/Side_effect) | Active Ingredient (en.wikipedia.org/wiki/Active_ingredient) | COVID-19 (en.wikipedia.org/wiki/Coronavirus_disease_2019) | SARS-CoV-2 (en.wikipedia.org/wiki/Severe_acute_respiratory…) | en.wikipedia.org/wiki/Virus | Drug Repurposing/Drug Repositioning (en.wikipedia.org/wiki/Drug_repositioning) | en.wikipedia.org/wiki/Toxicology | Virtual Screening (en.wikipedia.org/wiki/Virtual_screening) | en.wikipedia.org/wiki/Protein | en.wikipedia.org/wiki/Enzyme | en.wikipedia.org/wiki/Cell_(biology) | Replication (en.wikipedia.org/wiki/Viral_replication) | Inhibit (en.wikipedia.org/wiki/Enzyme_inhibitor) | en.wikipedia.org/wiki/DNA | Cell Membranes (en.wikipedia.org/wiki/Cell_membrane) | Amino Acid (en.wikipedia.org/wiki/Amino_acid) | en.wikipedia.org/wiki/RNA | en.wikipedia.org/wiki/Gene | Gene Expression (en.wikipedia.org/wiki/Gene_expression) | en.wikipedia.org/wiki/Genome | Lock and Key Model (en.wikipedia.org/wiki/Enzyme#%22Lock_and_key%2…) | en.wikipedia.org/wiki/Drug_discovery#Screening | Virtual Screening (en.wikipedia.org/wiki/Virtual_screening) | Dompé (dompe.com/en) | Parallel Process (en.wikipedia.org/wiki/Parallel_computing) | en.wikipedia.org/wiki/Abstraction_(computer_sc…) (PDB - Protein Data Bank (en.wikipedia.org/wiki/Protein_Data_Bank_(file_…))) | Bonding (en.wikipedia.org/wiki/Chemical_bond) | Experimental data (en.wikipedia.org/wiki/Experimental_data) (Proteins - accurate 3d data | Drug molecules - basic data) | X-Ray Diffraction (en.wikipedia.org/wiki/X-ray_crystallography#X-…) | NMR (en.wikipedia.org/wiki/Nuclear_magnetic_resonance) | Cryogenic Electron Microscopy (en.wikipedia.org/wiki/Cryogenic_electron_micro…) | Electromagnetic Force (en.wikipedia.org/wiki/Electromagnetism#Fundame…) | Van der Waals Force (en.wikipedia.org/wiki/Van_der_Waals_force) | Electrostatic Interaction (en.wikipedia.org/wiki/Coulomb%27s_law) | LiGen | Molecular Docking (en.wikipedia.org/wiki/Docking_(molecular)) | en.wikipedia.org/wiki/Toxicology | Few seconds per molecule for virtual screening

Molecular Dynamics Simulation
00:31:06
Molecular Dynamics Simulation (en.wikipedia.org/wiki/Molecular_dynamics) | Thermal effects (en.wikipedia.org/wiki/Temperature#Effects) | Stable State (en.wikipedia.org/wiki/Steady_state) | Statistical techniques (en.wikipedia.org/wiki/Statistics) | Numerical Simulation (en.wikipedia.org/wiki/Computer_simulation) | Newton's Laws of Motion (en.wikipedia.org/wiki/Newton%27s_laws_of_motion) | Bond vibration (en.wikipedia.org/wiki/Molecular_vibration) | Coulomb's law (en.wikipedia.org/wiki/Coulomb%27s_law) | Multi-Body Problem (en.wikipedia.org/wiki/Many-body_problem) | Unfold (en.wikipedia.org/wiki/Protein_folding) | Molecular dynamics simulation can take about a week | Clustering (en.wikipedia.org/wiki/Cluster_analysis) | Degrees of Freedom (en.wikipedia.org/wiki/Degrees_of_freedom) | Energy Surface (en.wikipedia.org/wiki/Potential_energy_surface) | Boltzmann Distribution (en.wikipedia.org/wiki/Boltzmann_distribution) | Virtual screening filtered ~400,000 possible drugs to ~7000 to go to the laboratory | en.wikipedia.org/wiki/Vaccine | Immune Response (en.wikipedia.org/wiki/Immune_response) | ~100 of ~7000 screened molecules were interesting | In Vitro Tests (en.wikipedia.org/wiki/In_vitro) | 40 effective molecules limited virus replication | en.wikipedia.org/wiki/Antiviral_drug | en.wikipedia.org/wiki/Cortisone

Computer Software and Hardware
01:09:44
en.wikipedia.org/wiki/GROMACS | Open Source (en.wikipedia.org/wiki/Open_source) | GPU (en.wikipedia.org/wiki/Graphics_processing_unit) | Homology Model (en.wikipedia.org/wiki/Homology_modeling) | C++ (en.wikipedia.org/wiki/C%2B%2B) | en.wikipedia.org/wiki/CUDA | Marconi 100 (top500.org/system/179845) | Galileo Linux Cluster (en.wikipedia.org/wiki/Galileo_(supercomputer)) | Eni (eni.com/en-IT/home.html) | HPC5 (eni.com/en-IT/operations/green-data-center-hpc…) | Nvidia V100 (en.wikipedia.org/wiki/Nvidia_Tesla) | en.wikipedia.org/wiki/Scheduling_(computing)

Results
01:20:24
en.wikipedia.org/wiki/Raloxifene | Clinical Trials (en.wikipedia.org/wiki/Clinical_trial) | Dimer (en.wikipedia.org/wiki/Protein_dimer) | en.wikipedia.org/wiki/Protease | Physical Chemistry (en.wikipedia.org/wiki/Physical_chemistry) | Computational Chemistry (en.wikipedia.org/wiki/Computational_chemistry) | Vector (Biology) (en.wikipedia.org/wiki/Vector_(molecular_biology)) | Vector (Mathematics) (en.wikipedia.org/wiki/Vector_(mathematics_and_…))

Bradykinin Storm Analysis
01:30:59
Dan Jacobson (linkedin.com/in/dan-jacobson-a593b720) | Computational Systems Biologist | Oak Ridge National Laboratory (en.wikipedia.org/wiki/Oak_Ridge_National_Labor…) (OLCF - Oak Ridge Leadership Computing Facility (en.wikipedia.org/wiki/Oak_Ridge_Leadership_Com…)) | Evolution (en.wikipedia.org/wiki/Viral_evolution) | en.wikipedia.org/wiki/Pathogen#Pathogenicity | 3D Structure (en.wikipedia.org/wiki/Molecular_geometry) | Human pathogenesis (en.wikipedia.org/wiki/Human_pathogen) | Demographic factors (en.wikipedia.org/wiki/Demography) | Bradykinin Storm Paper (elifesciences.org/articles/59177) | 17000 samples across 57 different tissues | Regulatory circuits (en.wikipedia.org/wiki/Genetic_regulatory_circuit) | Bronchoalveolar Lavage fluid (en.wikipedia.org/wiki/Bronchoalveolar_lavage) | Bronchoscope (en.wikipedia.org/wiki/Bronchoscopy) | Terminal Bronchioles (en.wikipedia.org/wiki/Bronchiole#Terminal_bron…) | Luminal surface (en.wikipedia.org/wiki/Lumen_(anatomy)) | Gas Exchange (en.wikipedia.org/wiki/Gas_exchange) | Pathways (en.wikipedia.org/wiki/Biological_pathway) (RAS - Renin-Angiotensin System …