{
 "cells": [
  {
   "cell_type": "markdown",
   "id": "e47686dc",
   "metadata": {},
   "source": [
    "## RNA droplets \n",
    "RNA origami design following the designs of Lorenzo Di Michele and Elisa Franco (https://doi.org/10.1038/s41565-024-01726-x, https://doi.org/10.1038/s41467-024-50003-x)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 1,
   "id": "951daf21",
   "metadata": {},
   "outputs": [],
   "source": [
    "import pyfurnace as pf\n",
    "\n",
    "uracil_connect = pf.Motif.from_structure('.&.', 'U&U')"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "f982220d",
   "metadata": {},
   "source": [
    "### Droplet A with Malachite Green aptamer"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "id": "e8487b0b",
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "                                                                             ╭──────────╮\n",
      "           ╭NNNKNNNNNNCC───CG─A──CUGNNNNKNNNNNU─────NNNKNNNKNNNNNKNNNNNNKNNNN┼─AUCGCGAAA╯\n",
      "           │┊┊┊┊┊┊┊┊┊┊┊┊   ┊┊    ┊┊┊┊┊┊┊┊┊┊┊┊┊      ┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊│           \n",
      "╭AAAGCGCUA─┼NNNKNNNNNNGGUAAGCAAUGGACNNNNKNNNNN─U╮╭──NNNKNNNKNNNNNKNNNNNNKNNNN╯           \n",
      "╰──────────╯                                    ││                                       \n",
      "                                                ││                                       \n",
      "                                                ↑↓                                       \n",
      "                                                ││                           ╭──────────╮\n",
      "               ╭NNNNKNNNNNNNN─3 5─NNNKNNNKNNNN──╯╰U─NNNKNNNNNKNNNNKNNNNKNNNNN┼─AUCGCGAAA╯\n",
      "               │┊┊┊┊┊┊┊┊┊┊┊┊┊     ┊┊┊┊┊┊┊┊┊┊┊┊      ┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊│           \n",
      "    ╭AAAGCGCUA─┼NNNNKNNNNNNNN─────NNNKNNNKNNNN─────UNNNKNNNNNKNNNNKNNNNKNNNNN╯           \n",
      "    ╰──────────╯                                                                         \n"
     ]
    }
   ],
   "source": [
    "kl = pf.KissingLoop(sequence='AUCGCGAAA')\n",
    "\n",
    "line0 = [kl.copy(),\n",
    "         pf.Stem(10),\n",
    "         pf.MalachiteGreenShort(),\n",
    "         pf.Stem(10),\n",
    "         uracil_connect.copy(),\n",
    "         pf.Dovetail(0, up_cross=False),\n",
    "         pf.Stem(25),\n",
    "         kl.copy().flip(),\n",
    "         ]\n",
    "\n",
    "line1 = [kl.copy(),\n",
    "         pf.Stem(13),\n",
    "         pf.start_end_stem(),\n",
    "         pf.Stem(12),\n",
    "         pf.Dovetail(0, down_cross=False),\n",
    "         uracil_connect.copy(),\n",
    "         pf.Stem(25),\n",
    "         kl.copy().flip(),\n",
    "        ]\n",
    "\n",
    "drop_a = pf.Origami(line0, line1, align='first')\n",
    "\n",
    "print(drop_a)"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "3d5f5759",
   "metadata": {},
   "source": [
    "### Droplet B with Broccoli aptamer"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "id": "df1960f5",
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "                                                                                          ╭──────────╮\n",
      "           ╭NNNKNNNNNNGGAGAC────GGUCGGG─UC────CAGNNNNKNNNNNU─────NNNKNNNKNNNNNKNNNNNNKNNNN┼─AGUCGACAA╯\n",
      "           │┊┊┊┊┊┊┊┊┊┊┊┊┊┊ ┊    ┊ ┊┊ ┊  ┊┊    ┊┊┊┊┊┊┊┊┊┊┊┊┊      ┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊│           \n",
      "╭AACAGCUGA─┼NNNKNNNNNNCCUCGG─GUGUGAGAUG─AG─CU─GUCNNNNKNNNNN─U╮╭──NNNKNNNKNNNNNKNNNNNNKNNNN╯           \n",
      "╰──────────╯                                                 ││                                       \n",
      "                                                             ││                                       \n",
      "                                                             ↑↓                                       \n",
      "                                                             ││                           ╭──────────╮\n",
      "                            ╭NNNNKNNNNNNNN─3 5─NNNKNNNKNNNN──╯╰U─NNNKNNNNNKNNNNKNNNNKNNNNN┼─AGUCGACAA╯\n",
      "                            │┊┊┊┊┊┊┊┊┊┊┊┊┊     ┊┊┊┊┊┊┊┊┊┊┊┊      ┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊┊│           \n",
      "                 ╭AACAGCUGA─┼NNNNKNNNNNNNN─────NNNKNNNKNNNN─────UNNNKNNNNNKNNNNKNNNNKNNNNN╯           \n",
      "                 ╰──────────╯                                                                         \n"
     ]
    }
   ],
   "source": [
    "kl_b_seq = 'AGUCGACAA'\n",
    "\n",
    "drop_b = drop_a.copy()\n",
    "\n",
    "drop_b[0, 2] = pf.Broccoli()\n",
    "\n",
    "# insert the sequence of the kissing loop B\n",
    "for i in (0, -1):\n",
    "    for j in (0, -1):\n",
    "        drop_b[i, j].set_sequence(kl_b_seq)\n",
    "\n",
    "print(drop_b)"
   ]
  }
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