{ "cells": [ { "cell_type": "markdown", "metadata": {}, "source": [ "# Covid-19 Spike Protein Example 1: Residue Neighborhoods" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "In this notebook, we use mdciao to analyze publicly available MD data of the Covid-19 Spike Protein, curated in the impressive [**COVID-19 Molecular Structure and Therapeutics Hub**](https://covid.molssi.org) put together by the [Molecular Sciences Software Institute (molSSI)](https://covid.molssi.org/). \n", "\n", "In particular, we use the data generated in the [Chodera-Lab](https://www.choderalab.org/) by Ivy Zhang, consisting of\n", "[Folding@home simulations of the SARS-CoV-2 spike RBD bound to human ACE2 (725.3 µs )](https://covid.molssi.org//simulations/#foldinghome-simulations-of-the-sars-cov-2-spike-rbd-bound-to-human-ace2). We quote:\n", "\n", "> All-atom MD simulations of the SARS-CoV-2 spike protein receptor binding domain (RBD) bound to human angiotensin converting enzyme-related carboypeptidase (ACE2), simulated using Folding@Home. The “wild-type” RBD and three mutants (N439K, K417V, and the double mutant N439K/K417V) were simulated. \n", "... \n", "RUNs denote different RBD mutants: N439K (RUN0), K417V (RUN1), N439K/K417V (RUN2), and WT (RUN3). CLONEs denote different independent replica trajectories" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "## Goals" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "We are going to use ``mdciao`` to compare the effect of the above mutations on the mutated residues's vicinities or *neighborhoods*. This is rather simple:\n", "\n", "1. Compute the residue neighborhoods for the mutated positions ``N439`` and ``K417`` in all four datasets, using [mdciao.cli.residue_neighborhoods](https://proteinformatics.uni-leipzig.de/mdciao/api/generated/generated/mdciao.cli.residue_neighborhoods.html)\n", "\n", "2. Compare these neighborhoods using [mdciao.cli.compare](https://proteinformatics.uni-leipzig.de/mdciao/api/generated/generated/mdciao.cli.compare.html) for changes in the residue-residue contacts." ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "## Residues of Interest and Molecular Topology\n", "Since we're not really familiar with the dataset, we can do several things to ease us into the data. Most helpful is to visualize one sample file in 3D, using the awesome [nglviewer](https://github.com/nglviewer/) and [mdtraj](https://mdtraj.org/). We can visually inspect the setup, its components etc:\n", "\n", "