scripts/3_experiment_generation/make_HADDOCK_experiments.ipynb

{
 "cells": [
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# Make HADDOCK Experiments\n",
    "## Generate run.params, AIR files, and copy resources."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 11,
   "metadata": {},
   "outputs": [],
   "source": [
    "import shutil, os, sys, time\n",
    "import pandas as pd"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 12,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>antibody_id</th>\n",
       "      <th>antibody_portion</th>\n",
       "      <th>antibody_sequence_source</th>\n",
       "      <th>antigen</th>\n",
       "      <th>h_chain_version</th>\n",
       "      <th>l_chain_version</th>\n",
       "      <th>h_chain</th>\n",
       "      <th>l_chain</th>\n",
       "      <th>antibody_pdb_path_original</th>\n",
       "      <th>antibody_pdb_path_renumbered</th>\n",
       "      <th>...</th>\n",
       "      <th>haddock_AIRviol</th>\n",
       "      <th>haddock_AIRviol_sd</th>\n",
       "      <th>haddock_dihedviol</th>\n",
       "      <th>haddock_dihedviol_sd</th>\n",
       "      <th>haddock_BSA</th>\n",
       "      <th>haddock_BSA_sd</th>\n",
       "      <th>haddock-score</th>\n",
       "      <th>haddock-score_sd</th>\n",
       "      <th>haddock_prodigy_deltaG_kcalpermol</th>\n",
       "      <th>haddock_prodigy_dissociation_constant_M</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>TUPPD1-001</td>\n",
       "      <td>Fv</td>\n",
       "      <td>EvoDiff, dd2169c, MSA_OA_DM_MAXSUB</td>\n",
       "      <td>PD1</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>EVQLVKSGAEFKKPNDSLKITCKASGYTFTNTGTNVHWVRQAPLKQ...</td>\n",
       "      <td>ELVPTQAIRSLSLFLSEGLKISCSSSRDIDNSSNINTELGSFHTRP...</td>\n",
       "      <td>./docking/inputs/PDBs/diffused_antibodies/comb...</td>\n",
       "      <td>./docking/inputs/PDBs/diffused_antibodies/comb...</td>\n",
       "      <td>...</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>TUPPD1-002</td>\n",
       "      <td>Fv</td>\n",
       "      <td>EvoDiff, dd2169c, MSA_OA_DM_MAXSUB</td>\n",
       "      <td>PD1</td>\n",
       "      <td>1</td>\n",
       "      <td>2</td>\n",
       "      <td>EVQLVKSGAEFKKPNDSLKITCKASGYTFTNTGTNVHWVRQAPLKQ...</td>\n",
       "      <td>DIIMTNTPTNLYVSPGESICIICRSSKSGFDGNLVHTYLKWYLQHP...</td>\n",
       "      <td>./docking/inputs/PDBs/diffused_antibodies/comb...</td>\n",
       "      <td>./docking/inputs/PDBs/diffused_antibodies/comb...</td>\n",
       "      <td>...</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>TUPPD1-003</td>\n",
       "      <td>Fv</td>\n",
       "      <td>EvoDiff, dd2169c, MSA_OA_DM_MAXSUB</td>\n",
       "      <td>PD1</td>\n",
       "      <td>1</td>\n",
       "      <td>3</td>\n",
       "      <td>EVQLVKSGAEFKKPNDSLKITCKASGYTFTNTGTNVHWVRQAPLKQ...</td>\n",
       "      <td>EIVMTQSPASLPVSPGERATVTCRASESVSDSANGRGWLAWLWQKP...</td>\n",
       "      <td>./docking/inputs/PDBs/diffused_antibodies/comb...</td>\n",
       "      <td>./docking/inputs/PDBs/diffused_antibodies/comb...</td>\n",
       "      <td>...</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>TUPPD1-004</td>\n",
       "      <td>Fv</td>\n",
       "      <td>EvoDiff, dd2169c, MSA_OA_DM_MAXSUB</td>\n",
       "      <td>PD1</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>QISLVESGPVLVKPNEQLKVACKTSGFTLSSYGTVLNWVRQAPGQR...</td>\n",
       "      <td>ELVPTQAIRSLSLFLSEGLKISCSSSRDIDNSSNINTELGSFHTRP...</td>\n",
       "      <td>./docking/inputs/PDBs/diffused_antibodies/comb...</td>\n",
       "      <td>./docking/inputs/PDBs/diffused_antibodies/comb...</td>\n",
       "      <td>...</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>TUPPD1-005</td>\n",
       "      <td>Fv</td>\n",
       "      <td>EvoDiff, dd2169c, MSA_OA_DM_MAXSUB</td>\n",
       "      <td>PD1</td>\n",
       "      <td>2</td>\n",
       "      <td>2</td>\n",
       "      <td>QISLVESGPVLVKPNEQLKVACKTSGFTLSSYGTVLNWVRQAPGQR...</td>\n",
       "      <td>DIIMTNTPTNLYVSPGESICIICRSSKSGFDGNLVHTYLKWYLQHP...</td>\n",
       "      <td>./docking/inputs/PDBs/diffused_antibodies/comb...</td>\n",
       "      <td>./docking/inputs/PDBs/diffused_antibodies/comb...</td>\n",
       "      <td>...</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>5 rows × 42 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "  antibody_id antibody_portion            antibody_sequence_source antigen  \\\n",
       "0  TUPPD1-001               Fv  EvoDiff, dd2169c, MSA_OA_DM_MAXSUB     PD1   \n",
       "1  TUPPD1-002               Fv  EvoDiff, dd2169c, MSA_OA_DM_MAXSUB     PD1   \n",
       "2  TUPPD1-003               Fv  EvoDiff, dd2169c, MSA_OA_DM_MAXSUB     PD1   \n",
       "3  TUPPD1-004               Fv  EvoDiff, dd2169c, MSA_OA_DM_MAXSUB     PD1   \n",
       "4  TUPPD1-005               Fv  EvoDiff, dd2169c, MSA_OA_DM_MAXSUB     PD1   \n",
       "\n",
       "   h_chain_version  l_chain_version  \\\n",
       "0                1                1   \n",
       "1                1                2   \n",
       "2                1                3   \n",
       "3                2                1   \n",
       "4                2                2   \n",
       "\n",
       "                                             h_chain  \\\n",
       "0  EVQLVKSGAEFKKPNDSLKITCKASGYTFTNTGTNVHWVRQAPLKQ...   \n",
       "1  EVQLVKSGAEFKKPNDSLKITCKASGYTFTNTGTNVHWVRQAPLKQ...   \n",
       "2  EVQLVKSGAEFKKPNDSLKITCKASGYTFTNTGTNVHWVRQAPLKQ...   \n",
       "3  QISLVESGPVLVKPNEQLKVACKTSGFTLSSYGTVLNWVRQAPGQR...   \n",
       "4  QISLVESGPVLVKPNEQLKVACKTSGFTLSSYGTVLNWVRQAPGQR...   \n",
       "\n",
       "                                             l_chain  \\\n",
       "0  ELVPTQAIRSLSLFLSEGLKISCSSSRDIDNSSNINTELGSFHTRP...   \n",
       "1  DIIMTNTPTNLYVSPGESICIICRSSKSGFDGNLVHTYLKWYLQHP...   \n",
       "2  EIVMTQSPASLPVSPGERATVTCRASESVSDSANGRGWLAWLWQKP...   \n",
       "3  ELVPTQAIRSLSLFLSEGLKISCSSSRDIDNSSNINTELGSFHTRP...   \n",
       "4  DIIMTNTPTNLYVSPGESICIICRSSKSGFDGNLVHTYLKWYLQHP...   \n",
       "\n",
       "                          antibody_pdb_path_original  \\\n",
       "0  ./docking/inputs/PDBs/diffused_antibodies/comb...   \n",
       "1  ./docking/inputs/PDBs/diffused_antibodies/comb...   \n",
       "2  ./docking/inputs/PDBs/diffused_antibodies/comb...   \n",
       "3  ./docking/inputs/PDBs/diffused_antibodies/comb...   \n",
       "4  ./docking/inputs/PDBs/diffused_antibodies/comb...   \n",
       "\n",
       "                        antibody_pdb_path_renumbered  ... haddock_AIRviol  \\\n",
       "0  ./docking/inputs/PDBs/diffused_antibodies/comb...  ...             NaN   \n",
       "1  ./docking/inputs/PDBs/diffused_antibodies/comb...  ...             NaN   \n",
       "2  ./docking/inputs/PDBs/diffused_antibodies/comb...  ...             NaN   \n",
       "3  ./docking/inputs/PDBs/diffused_antibodies/comb...  ...             NaN   \n",
       "4  ./docking/inputs/PDBs/diffused_antibodies/comb...  ...             NaN   \n",
       "\n",
       "  haddock_AIRviol_sd haddock_dihedviol haddock_dihedviol_sd haddock_BSA  \\\n",
       "0                NaN               NaN                  NaN         NaN   \n",
       "1                NaN               NaN                  NaN         NaN   \n",
       "2                NaN               NaN                  NaN         NaN   \n",
       "3                NaN               NaN                  NaN         NaN   \n",
       "4                NaN               NaN                  NaN         NaN   \n",
       "\n",
       "  haddock_BSA_sd haddock-score haddock-score_sd  \\\n",
       "0            NaN           NaN              NaN   \n",
       "1            NaN           NaN              NaN   \n",
       "2            NaN           NaN              NaN   \n",
       "3            NaN           NaN              NaN   \n",
       "4            NaN           NaN              NaN   \n",
       "\n",
       "  haddock_prodigy_deltaG_kcalpermol  haddock_prodigy_dissociation_constant_M  \n",
       "0                               NaN                                      NaN  \n",
       "1                               NaN                                      NaN  \n",
       "2                               NaN                                      NaN  \n",
       "3                               NaN                                      NaN  \n",
       "4                               NaN                                      NaN  \n",
       "\n",
       "[5 rows x 42 columns]"
      ]
     },
     "execution_count": 12,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "candidates = pd.read_excel(\"../../PD1_Candidates.xlsx\")\n",
    "candidates.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 13,
   "metadata": {},
   "outputs": [],
   "source": [
    "## Define function for creating AIR files\n",
    "def write_air_file(active1, passive1, active2, passive2, segid1='A', segid2='B', output_file=\"air.tbl\"):\n",
    "    with open(output_file, \"w\") as output_file:\n",
    "        ## Convert residues to integers\n",
    "        active1 = [int(x) for x in active1]\n",
    "        passive1 = [int(x) for x in passive1]\n",
    "        active2 = [int(x) for x in active2]\n",
    "        passive2 = [int(x) for x in passive2]\n",
    "        all1 = active1 + passive1\n",
    "        all2 = active2 + passive2\n",
    "\n",
    "        ## Write lines from the active1 list\n",
    "        for resi1 in active1:\n",
    "            output_file.write('assign (resi {:d} and segid {:s})'.format(resi1, segid1) + '\\n')\n",
    "            output_file.write('(\\n')\n",
    "            c = 0\n",
    "            for resi2 in all2:\n",
    "                output_file.write('       (resi {:d} and segid {:s})'.format(resi2, segid2) + '\\n')\n",
    "                c += 1\n",
    "                if c != len(all2):\n",
    "                    output_file.write('        or\\n')\n",
    "            output_file.write(') 2.0 2.0 0.0\\n\\n')\n",
    "\n",
    "        ## Write lines from the active2 list\n",
    "        for resi2 in active2:\n",
    "            output_file.write('assign (resi {:d} and segid {:s})'.format(resi2, segid2) + '\\n')\n",
    "            output_file.write('(\\n')\n",
    "            c = 0\n",
    "            for resi1 in all1:\n",
    "                output_file.write('       (resi {:d} and segid {:s})'.format(resi1, segid1) + '\\n')\n",
    "                c += 1\n",
    "                if c != len(all1):\n",
    "                    output_file.write('        or\\n')\n",
    "            output_file.write(') 2.0 2.0 0.0\\n\\n')\n",
    "\n",
    "    ## File will be closed automatically when exiting the 'with' block\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 14,
   "metadata": {},
   "outputs": [],
   "source": [
    "## Define function for Making run.param files\n",
    "def write_run_params(ambig_tbl = None,\n",
    "                     haddock_dir = \"/root/haddock/haddock2.4-2021-01/\",\n",
    "                     n_comp = 2,\n",
    "                     pdb_file_1 = \"\",\n",
    "                     pdb_file_2 = \"\",\n",
    "                     project_dir = \"./\",\n",
    "                     prot_segid_1 = \"A\",\n",
    "                     prot_segid_2 = \"B\",\n",
    "                     run_number = 1,\n",
    "                     output_file = \"run.param\"):\n",
    "    param_lines  = [\n",
    "        f\"HADDOCK_DIR={haddock_dir}\",\n",
    "        f\"N_COMP={n_comp}\",\n",
    "        f\"PDB_FILE1={pdb_file_1}\",\n",
    "        f\"PDB_FILE2={pdb_file_2}\",\n",
    "        f\"PROJECT_DIR={project_dir}\",\n",
    "        f\"PROT_SEGID_1={prot_segid_1}\",\n",
    "        f\"PROT_SEGID_2={prot_segid_2}\",\n",
    "        f\"RUN_NUMBER={run_number}\",\n",
    "    ]\n",
    "    if ambig_tbl:\n",
    "        param_lines = [f\"AMBIG_TBL={ambig_tbl}\", *param_lines]\n",
    "        \n",
    "    f = open(output_file, \"w\")\n",
    "    f.writelines(\"\\n\".join(param_lines))\n",
    "    f.close()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 15,
   "metadata": {},
   "outputs": [],
   "source": [
    "## Make experiment folders\n",
    "for index, candidate in candidates.iterrows():\n",
    "    candidate_id = candidate['antibody_id']\n",
    "    candidate_path = f\"../../docking/inputs/experiments/{candidate_id}/\"\n",
    "    os.makedirs(candidate_path, exist_ok=True)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 16,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Writing AIR file for TUPPD1-001...\n",
      "Writing AIR file for TUPPD1-002...\n",
      "Writing AIR file for TUPPD1-003...\n",
      "Writing AIR file for TUPPD1-004...\n",
      "Writing AIR file for TUPPD1-005...\n",
      "Writing AIR file for TUPPD1-006...\n",
      "Writing AIR file for TUPPD1-007...\n",
      "Writing AIR file for TUPPD1-008...\n",
      "Writing AIR file for TUPPD1-009...\n",
      "Writing AIR file for Acrixolimab...\n",
      "Writing AIR file for Balstilimab...\n",
      "Writing AIR file for Budigalimab...\n",
      "Writing AIR file for Camrelizumab...\n",
      "Writing AIR file for Cemiplimab...\n",
      "Writing AIR file for Cetrelimab...\n",
      "Writing AIR file for Dostarlimab...\n",
      "Writing AIR file for Enlonstobart...\n",
      "Writing AIR file for Eurestobart...\n",
      "Writing AIR file for Ezabenlimab...\n",
      "Writing AIR file for Finotonlimab...\n",
      "Writing AIR file for Geptanolimab...\n",
      "Writing AIR file for Iparomlimab...\n",
      "Writing AIR file for Lipustobart...\n",
      "Writing AIR file for Nivolumab...\n",
      "Writing AIR file for Nofazinlimab...\n",
      "Writing AIR file for Pembrolizumab...\n",
      "Writing AIR file for Penpulimab...\n",
      "Writing AIR file for Perenostobart...\n",
      "Writing AIR file for Peresolimab...\n",
      "Writing AIR file for Pidilizumab...\n",
      "Writing AIR file for Pimivalimab...\n",
      "Writing AIR file for Pradusinstobart...\n",
      "Writing AIR file for Pucotenlimab...\n",
      "Writing AIR file for Retifanlimab...\n",
      "Writing AIR file for Rosnilimab...\n",
      "Writing AIR file for Sasanlimab...\n",
      "Writing AIR file for Serplulimab...\n",
      "Writing AIR file for Sintilimab...\n",
      "Writing AIR file for Spartalizumab...\n",
      "Writing AIR file for Tislelizumab...\n",
      "Writing AIR file for Toripalimab...\n",
      "Writing AIR file for Zeluvalimab...\n"
     ]
    }
   ],
   "source": [
    "## Write AIR file for each candidate using active and passive residues\n",
    "for index, candidate in candidates.iterrows():\n",
    "    candidate_id = candidate['antibody_id']\n",
    "    target_id = \"PD1\"\n",
    "    active1 = candidate['antibody_active_residues'].replace('`','').split(',')\n",
    "    passive1 = []\n",
    "    active2 = candidate['antigen_active_residues'].replace('`','').split(',')\n",
    "    passive2 = []\n",
    "    candidate_path = f\"../../docking/inputs/experiments/{candidate_id}/\"\n",
    "    air_file_name = f\"{candidate_id}-{target_id}_air.tbl\"\n",
    "    print(f\"Writing AIR file for {candidate_id}...\")\n",
    "    write_air_file(active1, passive1, active2, passive2, segid1='A', segid2='B', output_file = f\"{candidate_path}{air_file_name}\")\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 17,
   "metadata": {},
   "outputs": [],
   "source": [
    "## Write run.param file for each candidate\n",
    "for index, candidate in candidates.iterrows():\n",
    "    candidate_id = candidate['antibody_id']\n",
    "    target_id = \"PD1\"\n",
    "    candidate_path = f\"../../docking/inputs/experiments/{candidate_id}/\"\n",
    "    write_run_params(ambig_tbl = f\"{candidate_id}-{target_id}_air.tbl\",\n",
    "                     haddock_dir = \"/root/haddock/haddock2.4-2021-01/\",\n",
    "                     n_comp = 2,\n",
    "                     pdb_file_1 = f\"./{candidate_id}_renumberedLplus1000.pdb\",\n",
    "                     pdb_file_2 = \"./5jxe_pd1.pdb\",\n",
    "                     project_dir = \"./\",\n",
    "                     prot_segid_1 = \"A\",\n",
    "                     prot_segid_2 = \"B\",\n",
    "                     run_number = 1,\n",
    "                     output_file = f\"{candidate_path}run.param\")"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 19,
   "metadata": {},
   "outputs": [],
   "source": [
    "## Copy HADDOCK Scripts and Target PDB to each candidate directory\n",
    "for index, candidate in candidates.iterrows():\n",
    "    candidate_id = candidate['antibody_id']\n",
    "    candidate_path = f\"../../docking/inputs/experiments/{candidate_id}/\"\n",
    "    shutil.copyfile(\"./haddock_resources/run-docking.csh\", f\"{candidate_path}run-docking.csh\")\n",
    "    shutil.copytree(\"./haddock_resources/ana_scripts\", f\"{candidate_path}ana_scripts\", dirs_exist_ok=True)\n",
    "    shutil.copyfile(\"../../docking/inputs/PDBs/antigens/PD1/5jxe_pd1.pdb\", f\"{candidate_path}5jxe_pd1.pdb\")\n",
    "    shutil.copyfile(\"./haddock_resources/cleanup.py\", f\"{candidate_path}cleanup.py\")\n",
    "    if \"TUPPD1\" in candidate_id:\n",
    "        shutil.copyfile(f\"../../docking/inputs/PDBs/diffused_antibodies/combined/{candidate_id}/{candidate_id}_renumberedLplus1000.pdb\", f\"{candidate_path}{candidate_id}_renumberedLplus1000.pdb\")\n",
    "    else:\n",
    "        shutil.copyfile(f\"../../docking/inputs/PDBs/reference_antibodies/{candidate_id}_renumberedLplus1000.pdb\", f\"{candidate_path}{candidate_id}_renumberedLplus1000.pdb\")"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": []
  }
 ],
 "metadata": {
  "kernelspec": {
   "display_name": "Python 3",
   "language": "python",
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