Enzyme by Ciro Santilli 40 Updated 2025-07-16
For an initial concrete example, consider e. Coli K-12 MG1655 gene thrA.
Video 1.
How Enzymes Work by RCSBProteinDataBank (2017)
Source. Shows in detail how aconitase catalyses the citrate to isocitrate reaction in the citric acid cycle.
Direct translation from oldest documents deemed reliable, originally in a mixture of Hebrew, Aramaic, and Greek. Interesting project.
This is notably opposed to the approach taken by many versions which were based on the Septuagint, which was a much earlier full-Greek translation.
  • reconstruction/ecoli/flat/condition/nutrient/minimal.tsv contains the nutrients in a minimal environment in which the cell survives:
    "molecule id" "lower bound (units.mmol / units.g / units.h)" "upper bound (units.mmol / units.g / units.h)"
    "ADP[c]" 3.15 3.15
    "PI[c]" 3.15 3.15
    "PROTON[c]" 3.15 3.15
    "GLC[p]" NaN 20
    "OXYGEN-MOLECULE[p]" NaN NaN
    "AMMONIUM[c]" NaN NaN
    "PI[p]" NaN NaN
    "K+[p]" NaN NaN
    "SULFATE[p]" NaN NaN
    "FE+2[p]" NaN NaN
    "CA+2[p]" NaN NaN
    "CL-[p]" NaN NaN
    "CO+2[p]" NaN NaN
    "MG+2[p]" NaN NaN
    "MN+2[p]" NaN NaN
    "NI+2[p]" NaN NaN
    "ZN+2[p]" NaN NaN
    "WATER[p]" NaN NaN
    "CARBON-DIOXIDE[p]" NaN NaN
    "CPD0-1958[p]" NaN NaN
    "L-SELENOCYSTEINE[c]" NaN NaN
    "GLC-D-LACTONE[c]" NaN NaN
    "CYTOSINE[c]" NaN NaN
    If we compare that to reconstruction/ecoli/flat/condition/nutrient/minimal_plus_amino_acids.tsv, we see that it adds the 20 amino acids on top of the minimal condition:
    "L-ALPHA-ALANINE[p]" NaN NaN
    "ARG[p]" NaN NaN
    "ASN[p]" NaN NaN
    "L-ASPARTATE[p]" NaN NaN
    "CYS[p]" NaN NaN
    "GLT[p]" NaN NaN
    "GLN[p]" NaN NaN
    "GLY[p]" NaN NaN
    "HIS[p]" NaN NaN
    "ILE[p]" NaN NaN
    "LEU[p]" NaN NaN
    "LYS[p]" NaN NaN
    "MET[p]" NaN NaN
    "PHE[p]" NaN NaN
    "PRO[p]" NaN NaN
    "SER[p]" NaN NaN
    "THR[p]" NaN NaN
    "TRP[p]" NaN NaN
    "TYR[p]" NaN NaN
    "L-SELENOCYSTEINE[c]" NaN NaN
    "VAL[p]" NaN NaN
    so we guess that NaN in the upper mound likely means infinite.
    We can try to understand the less obvious ones:
    • ADP: TODO
    • PI: TODO
    • PROTON[c]: presumably a measure of pH
    • GLC[p]: glucose, this can be seen by comparing minimal.tsv with minimal_no_glucose.tsv
    • AMMONIUM: ammonium. This appears to be the primary source of nitrogen atoms for producing amino acids.
    • CYTOSINE[c]: hmmm, why is external cytosine needed? Weird.
  • reconstruction/ecoli/flat/reconstruction/ecoli/flat/condition/timeseries/ contains sequences of conditions for each time. For example:
    • reconstruction/ecoli/flat/reconstruction/ecoli/flat/condition/timeseries/000000_basal.tsv contains:
      "time (units.s)" "nutrients"
      0 "minimal"
      which means just using reconstruction/ecoli/flat/condition/nutrient/minimal.tsv until infinity. That is the default one used by runSim.py, as can be seen from ./out/manual/wildtype_000000/000000/generation_000000/000000/simOut/Environment/attributes/nutrientTimeSeriesLabel which contains just 000000_basal.
    • reconstruction/ecoli/flat/reconstruction/ecoli/flat/condition/timeseries/000001_cut_glucose.tsv is more interesting and contains:
      "time (units.s)" "nutrients"
      0 "minimal"
      1200 "minimal_no_glucose"
      so we see that this will shift the conditions half-way to a condition that will eventually kill the bacteria because it will run out of glucose and thus energy!
    Timeseries can be selected with --variant nutrientTimeSeries X Y, see also: run variants.
    We can use that variant with:
    VARIANT="condition" FIRST_VARIANT_INDEX=1 LAST_VARIANT_INDEX=1 python runscripts/manual/runSim.py
  • reconstruction/ecoli/flat/condition/condition_defs.tsv contains lines of form:
    "condition" "nutrients"                "genotype perturbations" "doubling time (units.min)" "active TFs"
    "basal"     "minimal"                  {}                       44.0                        []
    "no_oxygen" "minimal_minus_oxygen"     {}                       100.0                       []
    "with_aa"   "minimal_plus_amino_acids" {}                       25.0                        ["CPLX-125", "MONOMER0-162", "CPLX0-7671", "CPLX0-228", "MONOMER0-155"]
    • condition refers to entries in reconstruction/ecoli/flat/condition/condition_defs.tsv
    • nutrients refers to entries under reconstruction/ecoli/flat/condition/nutrient/, e.g. reconstruction/ecoli/flat/condition/nutrient/minimal.tsv or reconstruction/ecoli/flat/condition/nutrient/minimal_plus_amino_acids.tsv
    • genotype perturbations: there aren't any in the file, but this suggests that genotype modifications can also be incorporated here
    • doubling time: TODO experimental data? Because this should be a simulation output, right? Or do they cheat and fix doubling by time?
    • active TFs: this suggests that they are cheating transcription factors here, as those would ideally be functions of other more basic inputs
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