{ "cells": [ { "cell_type": "markdown", "metadata": { "slideshow": { "slide_type": "slide" } }, "source": [ "# Protein preparation" ] }, { "cell_type": "markdown", "metadata": { "slideshow": { "slide_type": "slide" } }, "source": [ "## What is protein preparation?" ] }, { "cell_type": "markdown", "metadata": { "slideshow": { "slide_type": "-" } }, "source": [ "The **protein preparation** phase, based on the PDB2PQR and propKa softwares, addresses e.g. the problems of assigning titration states at the user-chosen pH; flipping the side chains of HIS, ASN, and GLN residues; and optimizing the overall hydrogen bonding network. \n", "\n", "After preparing, the **build** phase takes a prepared system and applies the chosen forcefield in order to obtain simulation-ready input files." ] }, { "cell_type": "markdown", "metadata": { "slideshow": { "slide_type": "slide" } }, "source": [ "## Let's start" ] }, { "cell_type": "code", "execution_count": 1, "metadata": { "slideshow": { "slide_type": "-" } }, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ "\n", "Please cite HTMD: Doerr et al.(2016)JCTC,12,1845. \n", "https://dx.doi.org/10.1021/acs.jctc.6b00049\n", "Documentation: http://software.acellera.com/\n", "To update: conda update htmd -c acellera -c psi4\n", "\n", "You are on the latest HTMD version (unpackaged : /home/joao/maindisk/software/repos/Acellera/htmd/htmd).\n", "\n" ] } ], "source": [ "from htmd.ui import *\n", "config(viewer='ngl')" ] }, { "cell_type": "markdown", "metadata": { "slideshow": { "slide_type": "slide" } }, "source": [ "## Protein Preparation in HTMD" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "The system preparation phase is based on the PDB2PQR software. It \n", "includes the following steps (from the\n", "[PDB2PQR algorithm\n", "description](http://apbs-pdb2pqr.readthedocs.io/en/latest/pdb2pqr/invoking.html)):\n", "\n", " * Compute empirical pKa values for the residues' local environment (propKa)\n", " * Assign titration states at the user-chosen pH;\n", " * Flipping the side chains of HIS (including user defined HIS states), ASN, and GLN residues;\n", "\n", " * Rotating the sidechain hydrogen on SER, THR, TYR, and CYS (if available);\n", " * Determining the best placement for the sidechain hydrogen on neutral HIS, protonated GLU, and protonated ASP;\n", " * Optimizing all water hydrogens." ] }, { "cell_type": "markdown", "metadata": { "slideshow": { "slide_type": "slide" } }, "source": [ "The hydrogen bonding network calculations are performed by the\n", "[PDB2PQR](http://www.poissonboltzmann.org/) software package. The pKa\n", "calculations are performed by the [PROPKA\n", "3.1](https://github.com/jensengroup/propka-3.1) software packages.\n", "Please see the copyright, license and citation terms distributed with each.\n", "\n", "Note that this version was modified in order to use an \n", "externally-supplied propKa **3.1** (installed automatically via dependencies), whereas\n", "the original had propKa 3.0 *embedded*!\n", "\n", "The results of the function should be roughly equivalent of the system\n", "preparation wizard's preprocessing and optimization steps\n", "of Schrodinger's Maestro software." ] }, { "cell_type": "markdown", "metadata": { "slideshow": { "slide_type": "slide" } }, "source": [ "### Protein residue pKas in water" ] }, { "cell_type": "markdown", "metadata": { "slideshow": { "slide_type": "-" } }, "source": [ "
\n", " | resname | \n", "resid | \n", "pKa | \n", "protonation | \n", "
---|---|---|---|---|
0 | \n", "ILE | \n", "16 | \n", "NaN | \n", "ILE | \n", "
1 | \n", "VAL | \n", "17 | \n", "NaN | \n", "VAL | \n", "
2 | \n", "GLY | \n", "18 | \n", "NaN | \n", "GLY | \n", "
3 | \n", "GLY | \n", "19 | \n", "NaN | \n", "GLY | \n", "
4 | \n", "TYR | \n", "20 | \n", "9.590845 | \n", "TYR | \n", "
5 | \n", "THR | \n", "21 | \n", "NaN | \n", "THR | \n", "
6 | \n", "CYS | \n", "22 | \n", "99.990000 | \n", "CYX | \n", "
7 | \n", "GLY | \n", "23 | \n", "NaN | \n", "GLY | \n", "
8 | \n", "ALA | \n", "24 | \n", "NaN | \n", "ALA | \n", "
9 | \n", "ASN | \n", "25 | \n", "NaN | \n", "ASN | \n", "