Supplementary Table1: List of Class of molecule, Entity, their position and amount used for the inactivation of TPO activity in the presence of Drug (PTU)

S.No. / class / id / Name / PositionToCompartment / InitialQuantity
PROTEIN / s1 / Leptin / inside / 1
PROTEIN / s2 / TRH / inside / 0.5
PROTEIN / s3 / TSH / inside / 0.5
PROTEIN / s4 / TSHR / transmembrane / 1
PROTEIN / s10 / Na+/I- / transmembrane / 1
ION / s9 / e I- / inside / 2
ION / s11 / i I- / inside / 1
ION / s19 / Io / inside / 0
PROTEIN / s20 / TPO / inside / 2
SIMPLE_MOLECULE / s21 / cAMP / inside / 1
PROTEIN / s22 / TG / inside / 1
GENE / s23 / DNATG / inside / 1
RNA / s24 / m-RNA / inside / 1
SIMPLE_MOLECULE / s25 / T4 / inside / 2
SIMPLE_MOLECULE / s26 / T3 / inside / 1
PROTEIN / s27 / deiodinase / inside / 2
DRUG / s28 / PTU / inside / 1.5
DEGRADED / s30 / sa27_degraded / inside / 0
PROTEIN / s31 / in TPO / inside / 0

Supplementary Table 2:Details of different types of Kinetics with their units at value one for TPO model

S.No. / Id / Name / Units / Constant
kmc_re1_s1 / Michaelis constant of species s1 in reaction re1 / substance / TRUE
vmax_re1 / Forward maximal velocity of reaction re1 / substance_per_time / TRUE
kmc_re4_s10 / Michaelis constant of species s10 in reaction re4 / substance / TRUE
vmax_re4 / Forward maximal velocity of reaction re4 / substance_per_time / TRUE
kmc_re5_s9 / Michaelis constant of species s9 in reaction re5 / substance / TRUE
vmax_re5 / Forward maximal velocity of reaction re5 / substance_per_time / TRUE
kmc_re8_s11_s20 / Michaelis constant of species s11and enzyme s20 in reaction re8 / substance / TRUE
kcat_re8_s20 / Substrate catalytic rate constant of enzyme s20 in reaction re8 / per_second / TRUE
vmax_re10 / Forward maximal velocity of reaction re10 / substance_per_time / TRUE
ksp_re10_s23 / Half saturation constant of species DNATG and enzyme s23 in reaction re10 / substance / TRUE
hic_re10_s23 / Hill coefficient for enzyme s23 in reaction re10 / DIMENSIONLESS / TRUE
vmax_re11 / Forward maximal velocity of reaction re11 / substance_per_time / TRUE
ksp_re11_s24 / Half saturation constant of species m-RNA and enzyme s24 in reaction re11 / substance / TRUE
hic_re11_s24 / Hill coefficient for enzyme s24 in reaction re11 / dimensionless / TRUE
kmc_re12_s21 / Michaelis constant of species s21 in reaction re12 / substance / TRUE
vmax_re12 / Forward maximal velocity of reaction re12 / substance_per_time / TRUE
kmc_re14_s25_s27 / Michaelis constant of species s25and enzyme s27 in reaction re14 / substance / TRUE
kcat_re14_s27 / Substrate catalytic rate constant of enzyme s27 in reaction re14 / per_second / TRUE
kmc_re16_s19 / Michaelis constant of species s19 in reaction re16 / substance / TRUE
vmax_re16 / Forward maximal velocity of reaction re16 / substance_per_time / TRUE
kmc_re15_s22 / Michaelis constant of species s22 in reaction re15 / substance / TRUE
vmax_re15 / Forward maximal velocity of reaction re15 / substance_per_time / TRUE
kmc_re20_s2 / Michaelis constant of species s2 in reaction re20 / substance / TRUE
vmax_re20 / Forward maximal velocity of reaction re20 / substance_per_time / TRUE
kmc_re21_s3 / Michaelis constant of species s3 in reaction re21 / substance / TRUE
vmax_re21 / Forward maximal velocity of reaction re21 / substance_per_time / TRUE
kmc_re22_s4 / Michaelis constant of species s4 in reaction re22 / substance / TRUE
vmax_re22 / Forward maximal velocity of reaction re22 / substance_per_time / TRUE
kass_re23_s28 / Association constant of reaction re23 / per_second / TRUE
kmc_re25_s28 / Michaelis constant of species s28 in reaction re25 / substance / TRUE
vmax_re25 / Forward maximal velocity of reaction re25 / substance_per_time / TRUE

Supplementary Table 3: List of class of molecule, entity, their position and amount used for inactivation of TSHRactivity in the presence low molecular weight (Drug)

S.No. / Class / Id / Name / PositionToCompartment / InitialQuantity
PROTEIN / s1 / Leptin / inside / 1
PROTEIN / s2 / TRH / inside / 0.5
PROTEIN / s3 / TSH / inside / 1
PROTEIN / s4 / TSHR / transmembrane / 1
PROTEIN / s10 / Na+/I- / transmembrane / 2
ION / s9 / e I- / inside / 2
ION / s11 / i I- / inside / 1
ION / s19 / Io / inside / 0
PROTEIN / s20 / TPO / inside / 2
SIMPLE_MOLECULE / s21 / cAMP / inside / 1
PROTEIN / s22 / TG / inside / 1
GENE / s23 / DNATG / inside / 1
RNA / s24 / m-RNA / inside / 1
SIMPLE_MOLECULE / s25 / T4 / inside / 2
SIMPLE_MOLECULE / s26 / T3 / inside / 1
PROTEIN / s27 / deiodinase / inside / 2
DRUG / s35 / Drug / inside / 0.1, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0
DEGRADED / s36 / degradation / inside / 0
PROTEIN / s37 / in TSHR / transmembrane / 0

Supplementary Table 4: Details of different types of Kinetics with their units at value 1 for TSHR model

S.No. / Id / Name / Units / Constant
kmc_re1_s1 / Michaelis constant of species s1 in reaction re1 / substance / TRUE
vmax_re1 / Forward maximal velocity of reaction re1 / substance_per_time / TRUE
kmc_re4_s10 / Michaelis constant of species s10 in reaction re4 / substance / TRUE
vmax_re4 / Forward maximal velocity of reaction re4 / substance_per_time / TRUE
kmc_re8_s11_s20 / Michaelis constant of species s11and enzyme s20 in reaction re8 / substance / TRUE
kcat_re8_s20 / Substrate catalytic rate constant of enzyme s20 in reaction re8 / per_second / TRUE
kmc_re12_s21 / Michaelis constant of species s21 in reaction re12 / substance / TRUE
vmax_re12 / Forward maximal velocity of reaction re12 / substance_per_time / TRUE
kmc_re14_s25_s27 / Michaelis constant of species s25and enzyme s27 in reaction re14 / substance / TRUE
kcat_re14_s27 / Substrate catalytic rate constant of enzyme s27 in reaction re14 / per_second / TRUE
kmc_re16_s19 / Michaelis constant of species s19 in reaction re16 / substance / TRUE
vmax_re16 / Forward maximal velocity of reaction re16 / substance_per_time / TRUE
kmc_re15_s22 / Michaelis constant of species s22 in reaction re15 / substance / TRUE
vmax_re15 / Forward maximal velocity of reaction re15 / substance_per_time / TRUE
kmc_re20_s2 / Michaelis constant of species s2 in reaction re20 / substance / TRUE
vmax_re20 / Forward maximal velocity of reaction re20 / substance_per_time / TRUE
kmc_re21_s3 / Michaelis constant of species s3 in reaction re21 / substance / TRUE
vmax_re21 / Forward maximal velocity of reaction re21 / substance_per_time / TRUE
kmc_re22_s4 / Michaelis constant of species s4 in reaction re22 / substance / TRUE
vmax_re22 / Forward maximal velocity of reaction re22 / substance_per_time / TRUE
kass_re5_s10 / Association constant of reaction re5 / per_second / TRUE
kmc_re30_s35 / Michaelis constant of species s35 in reaction re30 / substance / TRUE
vmax_re30 / Forward maximal velocity of reaction re30 / substance_per_time / TRUE
kass_re10 / Association constant of reaction re10 / per_second / TRUE
kass_re11 / Association constant of reaction re11 / per_second / TRUE
kass_re31_s35 / Association constant of reaction re31 / per_second / TRUE

Supplementary Table 5:Details of rate kinetics equations for model targeting TSHR

S. No. / Reactions / Equations
Leptin -> TRH / vmax_re1 * Leptin / (kmc_re1_Leptin + Leptin)
TRH -> TSH / vmax_re20* TRH / (kmc_re20_TRH + TRH)
TSH -> TSHR / vmax_re21 * TSH / (kmc_re21_TSH + TSH)
TSHR -> cAMP / vmax_re22 * TSHR / (kmc_re22_TSHR + TSHR)
cAMP -> DNATG / vmax_re12 * cAMP / (kmc_re12_cAMP + cAMP)
DNATG -> m-RNA / vmax_re10* (DNATG ^hic_re10_ DNATG / (DNATG ^hic_re10_ DNATG + ksp_re10_DNATG ^hic_re10_ DNATG))
m-RNA -> TG / vmax_re11* (m-RNA ^hic_re11_m-RNA / (m-RNA ^hic_re11_ m-RNA + ksp_re11_s m-RNA ^hic_re11_ m-RNA))
Na+/I- -> Active Na+/I- / vmax_re4 * Na+/I- / (kmc_re4_ Na+/I- + Na+/I- )
Active TSHR -> Inactive TSHR catalyzed by Drug / kass_re31_Drug * Active TSHR * Drug * c1
eI- -> iI- / vmax_re5 * eI- / (kmc_re5_eI- + eI-)
iI- -> Io catalyzed by TPO / s20 * (kcat_re8_TPO * iI- / (kmc_re8_iI- _ TPO + iI-))
TG -> T4 / vmax_re16 * TG / (kmc_re16_ TG + TG)
Io –> T4 / vmax_re16 * Io / (kmc_re16_ Io + Io)
T4 -> T3 catalyzed by deiodinase / s27 * (kcat_re14_deiodinase* T4/ (kmc_re14_T4_deiodinase +T4))
Drug -> Degrade / vmax_re31 * Drug * c1 / (kmc_re31_ Drug + Drug * c1)

Supplementary Table 6: List of class of molecule, entity, their position and amount used for the inactivation of NIS activity in the presence of drug

S. No. / Class / Id / Name / PositionToCompartment / InitialQuantity
PROTEIN / s1 / Leptin / inside / 1
PROTEIN / s2 / TRH / inside / 0.5
PROTEIN / s3 / TSH / inside / 0.5
PROTEIN / s4 / TSHR / transmembrane / 1
PROTEIN / s10 / Na+/I- / transmembrane / 2
ION / s9 / e I- / inside / 2
ION / s11 / i I- / inside / 1
ION / s19 / Io / inside / 0
PROTEIN / s20 / TPO / inside / 2
SIMPLE_MOLECULE / s21 / cAMP / inside / 1
PROTEIN / s22 / TG / inside / 1
GENE / s23 / DNATG / inside / 1
RNA / s24 / m-RNA / inside / 1
SIMPLE_MOLECULE / s25 / T4 / inside / 2
SIMPLE_MOLECULE / s26 / T3 / inside / 1
PROTEIN / s27 / deiodinase / inside / 2
PROTEIN / s32 / in Na+/I- / transmembrane / 0
DRUG / s33 / Drug / inside / 0.1, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0
DEGRADED / s34 / sa32_degraded / inside / 0

Supplementary Table 7:Details of different types of Kinetics with their units at value 1 for TSHR model

S.No / id / Name / Units / Constant
kmc_re1_s1 / Michaelis constant of species s1 in reaction re1 / substance / TRUE
vmax_re1 / Forward maximal velocity of reaction re1 / substance_per_time / TRUE
kmc_re4_s10 / Michaelis constant of species s10 in reaction re4 / substance / TRUE
vmax_re4 / Forward maximal velocity of reaction re4 / substance_per_time / TRUE
kmc_re8_s11_s20 / Michaelis constant of species s11and enzyme s20 in reaction re8 / substance / TRUE
kcat_re8_s20 / Substrate catalytic rate constant of enzyme s20 in reaction re8 / per_second / TRUE
vmax_re10 / Forward maximal velocity of reaction re10 / substance_per_time / TRUE
ksp_re10_s23 / Half saturation constant of species DNATG and enzyme s23 in reaction re10 / substance / TRUE
hic_re10_s23 / Hill coefficient for enzyme s23 in reaction re10 / DIMENSIONLESS / TRUE
vmax_re11 / Forward maximal velocity of reaction re11 / substance_per_time / TRUE
ksp_re11_s24 / Half saturation constant of species m-RNA and enzyme s24 in reaction re11 / substance / TRUE
hic_re11_s24 / Hill coefficient for enzyme s24 in reaction re11 / DIMENSIONLESS / TRUE
kmc_re12_s21 / Michaelis constant of species s21 in reaction re12 / substance / TRUE
vmax_re12 / Forward maximal velocity of reaction re12 / substance_per_time / TRUE
kmc_re14_s25_s27 / Michaelis constant of species s25and enzyme s27 in reaction re14 / substance / TRUE
kcat_re14_s27 / Substrate catalytic rate constant of enzyme s27 in reaction re14 / per_second / TRUE
kmc_re16_s19 / Michaelis constant of species s19 in reaction re16 / substance / TRUE
vmax_re16 / Forward maximal velocity of reaction re16 / substance_per_time / TRUE
kmc_re15_s22 / Michaelis constant of species s22 in reaction re15 / substance / TRUE
vmax_re15 / Forward maximal velocity of reaction re15 / substance_per_time / TRUE
kmc_re20_s2 / Michaelis constant of species s2 in reaction re20 / substance / TRUE
vmax_re20 / Forward maximal velocity of reaction re20 / substance_per_time / TRUE
kmc_re21_s3 / Michaelis constant of species s3 in reaction re21 / substance / TRUE
vmax_re21 / Forward maximal velocity of reaction re21 / substance_per_time / TRUE
kmc_re22_s4 / Michaelis constant of species s4 in reaction re22 / substance / TRUE
vmax_re22 / Forward maximal velocity of reaction re22 / substance_per_time / TRUE
kmc_re28_s33 / Michaelis constant of species s33 in reaction re28 / substance / TRUE
vmax_re28 / Forward maximal velocity of reaction re28 / substance_per_time / TRUE
kass_re5_s10 / Association constant of reaction re5 / per_second / TRUE
kass_re26_s33 / Association constant of reaction re26 / per_second / TRUE

Supplementary Table 8:Details of Kinetics Equations for the Model when drug targeting NIS

S. No. / Reactions / Equations
Leptin -> TRH / vmax_re1 * Leptin/ (kmc_re1_ Leptin + Leptin)
TRH -> TSH / vmax_re20 * TRH / (kmc_re20_ TRH + TRH)
TSH -> TSHR / vmax_re21 * TSH / (kmc_re21_ TSH + TSH)
TSHR -> cAMP / vmax_re22 * TSHR / (kmc_r22_ TSHR + TSHR)
cAMP -> DNATG / vmax_re12 * cAMP / (kmc_re5_cAMP + cAMP)
DNATG -> m-RNA / vmax_re10 * (DNATG ^hic_re10_ DNATG / (DNATG ^hic_re10_ DNATG + ksp_re10_ DNATG ^hic_re10_ DNATG))
m-RNA -> TG / vmax_re11 * (m-RNA ^hic_re11_ m-RNA / (m-RNA ^hic_re11_ m-RNA + ksp_re11_s m-RNA ^hic_re11_ m-RNA))
Na+/I- -> Active Na+/I- / vmax_re4 * Na+/I- / (kmc_re4_ Na+/I- + Na+/I- )
Na+/I- -> in Na+/I- catalyzed by Hypothetical Drug / kass_re26_Drug * Na/I- * Drug * c1
eI- -> iI- / vmax_re5 * eI- / (kmc_re5_eI- + eI-)
iI- -> Io catalyzed by TPO / S8 * (kcat_re8_TPO * iI- / (kmc_re8_iI- _ TPO + iI-))
TG -> T4 / vmax_re15 * TG / (kmc_re15_ TG + TG)
Io –> T4 / vmax_re16 * Io / (kmc_re16_ Io + Io)
T4 -> T3 catalyzed by deiodinase / s27 * (kcat_re14_deiodinase* T4/ (kmc_re14_T4 _deiodinase +T4))
Drug -> Degrade / vmax_re28 * Drug * c1 / (kmc_re28_ Drug + Drug * c1)