01_molecule_representation.ipynb

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    "<div style=\"text-align:center;\">\n",
    "  <img src=\"custom/molssi_main_horizontal.png\" style=\"display: block; margin: 0 auto; max-height:200px;\">\n",
    "</div>\n",
    "\n",
    "\n",
    "# Digital Representation of Molecules\n",
    "\n",
    "<strong>Author(s):</strong> Jessica A. Nash, The Molecular Sciences Software Institute\n",
    "\n",
    "<div class=\"alert alert-block alert-info\"> \n",
    "<h2>Overview</h2>\n",
    "\n",
    "<strong>Questions:</strong>\n",
    "\n",
    "* How are molecules represented on computers?\n",
    "\n",
    "* What is a SMILES?\n",
    "    \n",
    "* What are common molecular file formats?\n",
    "\n",
    "<strong>Objectives:</strong>\n",
    "\n",
    "* Convert molecules from chemical formula and structures to SMILES strings.\n",
    "\n",
    "</div>\n",
    "\n",
    "In order to work with molecules in a programmatically, we have to be able to represent them on computers.\n",
    "This can be acheived many ways. \n",
    "One way is through something called a SMILES string.\n",
    "There are also file formats that represent molecules.\n",
    "Examples of file formats include ``pdb``, ``mol``, ``mol2``, ``cif``, and ``mmcif``."
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    "## Simplified Molecular-Input Line-entry System: SMILES \n",
    "\n",
    "SMILES stands for \"Simplified Molecular-Input Line-Entry System\" and is a way to represent molecules as a string of characters.\n",
    "\n",
    "Consider the molecule ethanol. The image below shows a representation that we are used to seeing in chemistry:\n",
    "\n",
    "![ethanol](images/ethanol.png)\n",
    "\n",
    "However, the SMILES representation of this molecule would be \"CCO\".\n",
    "\n",
    "You can read more about SMILES at [this tutorial](https://archive.epa.gov/med/med_archive_03/web/html/smiles.html), but rules for atoms and bonds are also repeated below.\n",
    "\n",
    "### Atoms\n",
    "SMILES supports all elements in the periodic table. An atom is represented using its respective atomic symbol. Upper case letters refer to non-aromatic atoms; lower case letters refer to aromatic atoms. If the atomic symbol has more than one letter the second letter must be lower case.\n",
    "\n",
    "### Bonds\n",
    "```\n",
    "-\tSingle bond\n",
    "=\tDouble bond\n",
    "#\tTriple bond\n",
    "*\tAromatic bond\n",
    ".\tDisconnected structures\n",
    "```\n",
    "Single bonds are the default and therefore need not be entered. For example, 'CC' would mean that there is a non-aromatic carbon attached to another non-aromatic carbon by a single bond, and the computer would identify the structure as the chemical ethane. It is also assumed that the bond between two lower case atom symbols is aromatic. A blank terminates the SMILES string.\n",
    "\n",
    "### Branches\n",
    "\n",
    "A branch from a chain is specified by placing the SMILES symbol(s) for the branch between parenthesis. Some examples:\n",
    "\n",
    "```\n",
    "\n",
    "CC(O)C\t2-Propanol\n",
    "CC(=O)C\t2-Propanone\n",
    "```\n",
    "\n",
    "### Rings\n",
    "\n",
    "A ring is specified by placing a number directly after the SMILES symbol where the ring closure occurs. This number acts as a marker, indicating that the atoms with the same number are connected, thus forming a ring. For instance:\n",
    "\n",
    "```\n",
    "C1CCCC1 cyclopentane\n",
    "n1ccccc1\tPyridine\n",
    "```\n",
    "\n",
    "### SMILES Examples\n",
    "\n",
    "<div style=\"text-align:center;\">\n",
    "  <img src=\"images/smiles_example_1.png\" style=\"display: block; margin: 0 auto; max-height:300px;\">\n",
    "</div>\n",
    "\n",
    "<div style=\"text-align:center;\">\n",
    "  <img src=\"images/smiles_example_2.png\" style=\"display: block; margin: 0 auto; max-height:300px;\">\n",
    "</div>\n",
    "\n",
    "### Using Online Resources\n",
    "Most of the time, you will not need to write a SMILES string by hand. You will be able to look up a molecule's SMILES string from a web database like [PubChem](https://pubchem.ncbi.nlm.nih.gov/).\n",
    "\n",
    "You can also use tools like this [molecule sketcher from the Protein Data Bank](https://www.rcsb.org/chemical-sketch)\n",
    "to draw molecules and get their SMILES strings."
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    "<div class=\"alert alert-block alert-warning\">\n",
    "<h3>Exercise</h3>\n",
    "\n",
    "<p> Based on what you've learned about SMILES strings, answer the following questions:\n",
    "<p>\n",
    "    <ul>\n",
    "        <li> What is the SMILES for ethanol?</li>\n",
    "        <li> What is the SMILES for water?</li>\n",
    "        <li> What is the SMILES for benzene?</li>\n",
    "        <li> What molecule is represented by the SMILES O=C=O?</li>\n",
    "        <li> What is the SMILES for an amide group?<//li>\n",
    "        <li> What is the SMILES for a 4 membered carbon chain with an amide group on the second carbon?</li>\n",
    "    </ul>\n",
    "</p>\n",
    "<p>Check your answers from this previous exercise using the PDB molecule sketcher. Notice that you can type in a SMILES string and have the sketcher draw the molecule for you.</p>\n",
    "\n",
    "</div>"
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    "# Fill in your answers here:\n",
    "# 1.\n",
    "# 2.\n",
    "# 3.\n",
    "# 4\n",
    "# 5.\n",
    "# 6."
   ]
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    "## Molecular File Formats\n",
    "\n",
    "Molecules can also be represented using a number of different file formats. As you work more in chemistry, you may see a number of these. Sometimes you will have to pick a file format based on the software you are using or the molecular information you want to save. \n",
    "\n",
    "| File Format | Description                                                                 | Features                                                              | Common Uses                              |\n",
    "|-------------|-----------------------------------------------------------------------------|-----------------------------------------------------------------------|------------------------------------------|\n",
    "| SMILES      | Simplified Molecular Input Line Entry System                                | Line notation for representing molecular structures                   | Database               |\n",
    "| InChI       | International Chemical Identifier                                           | Textual identifier for chemical substances                            | Databases             |\n",
    "| MOL/SDF     | MDL MOLfile and Structure-Data File                                         | Contains 2D/3D coordinates, atoms, bonds                              | Structure visualization, cheminformatics |\n",
    "| PDB         | Protein Data Bank format                                                    | Often used for 3D structures of proteins and nucleic acids,but can also be used for small molecules. Often does not contain molecule information, and cannot store partial charges.                           | Structural biology, bioinformatics       |\n",
    "| XYZ         | Cartesian coordinates                                                       | Simple text format with atom types and 3D coordinates                 | Computational chemistry, molecular dynamics |     |\n",
    "| CIF         | Crystallographic Information File                                           | Text file format for representing crystal structure data              | Crystallography                          |\n",
    "| PQR         | Extended PDB format with partial charges and radii                          | Includes atomic coordinates, partial charges, and radii               | Electrostatics calculations              |\n",
    "| PDBQT       | PDB format with torsion angles and charges used in AutoDock                 | Includes atomic coordinates, partial charges, torsion angles          | Molecular docking                        |\n",
    "|MOL2   |Tripos Mol2 format|\tContains atomic coordinates, bonds, molecule types, substructures, and partial charges|\tMolecular modeling, cheminformatics, computational chemistry\n"
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