diff --git a/examples/sample/Rb2.7.vcml b/examples/sample/Rb2.7.vcml new file mode 100644 index 0000000..fdb0af4 --- /dev/null +++ b/examples/sample/Rb2.7.vcml @@ -0,0 +1,90 @@ + +0.11.0(0.1 * k)(0.1 * k)(0.1 * k)(0.1 * k)(10.0 * k)(100.0 * k)(10.0 * k)(15.0 * k)(100.0 * k)(0.1 * k)(10.0 * k)(DP1_E2F1_Rbppu_HDAC1_SWI_SNFu + DP1_E2F1_Rbpuu_HDAC1_SWI_SNFu + DP1_E2F1_Rbupu_HDAC1_SWI_SNFu + DP1_E2F1_Rbuuu_HDAC1_SWI_SNFu + DP1_E2F1_Rbuuu_HDAC1_SUV39H1_HP1gamma_SWI_SNFu)HDAC1SWI_SNFpDP1_E2F1_Rbppu_SWI_SNFuSUV39H1_HP1gammaDP1_E2F1_RbuuuDP1_E2F1_RbpppSWI_SNFuDP1_E2F1_RbpupDP1_E2F1_Rbpuu_SWI_SNFuDP1_E2F1_RbuppDP1_E2F1_Rbupu_SWI_SNFuDP1_E2F1_RbppuDP1_E2F1_Rbppp_SWI_SNFpDP1_E2F1_Rbppu_HDAC1_SWI_SNFuDP1_E2F1_RbuupDP1_E2F1_Rbuuu_SWI_SNFuDP1_E2F1_RbpuuDP1_E2F1_Rbpup_SWI_SNFpDP1_E2F1_Rbpuu_HDAC1_SWI_SNFuDP1_E2F1_RbupuDP1_E2F1_Rbupp_SWI_SNFpDP1_E2F1_Rbupu_HDAC1_SWI_SNFuDP1_E2F1_Rbppu_SWI_SNFpDP1_E2F1_Rbppp_SWI_SNFuDP1_E2F1_Rbuup_SWI_SNFpDP1_E2F1_Rbuuu_HDAC1_SWI_SNFuDP1_E2F1_Rbpuu_SWI_SNFpDP1_E2F1_Rbpup_SWI_SNFuDP1_E2F1_Rbupu_SWI_SNFpDP1_E2F1_Rbupp_SWI_SNFuDP1_E2F1_Rbuuu_SWI_SNFpDP1_E2F1_Rbuup_SWI_SNFuDP1_E2F1_Rbuuu_HDAC1_SUV39H1_HP1gamma_SWI_SNFu(rateParam3 * DP1_E2F1_Rbpuu_SWI_SNFp / cell)(rateParam3 * DP1_E2F1_Rbpup_SWI_SNFu / cell)(rateParam4 * DP1_E2F1_Rbuup_SWI_SNFp / cell)(rateParam4 * DP1_E2F1_Rbpup_SWI_SNFu / cell)(rateParam4 * DP1_E2F1_Rbupp_SWI_SNFu / cell)(rateParam9 * DP1_E2F1_Rbpuu_SWI_SNFp / cell)(rateParam9 * DP1_E2F1_Rbupu_SWI_SNFp / cell)(rateParam12 * SUV39H1_HP1gamma * DP1_E2F1_Rbuuu_HDAC1_SWI_SNFu / cell)(rateParam4 * DP1_E2F1_Rbuup_SWI_SNFu / cell)(rateParam9 * DP1_E2F1_Rbuuu_SWI_SNFp / cell)(k * DP1_E2F1_Rbuuu_HDAC1_SUV39H1_HP1gamma_SWI_SNFu / cell)(k * DP1_E2F1_Rbuuu_HDAC1_SWI_SNFu / cell)(rateParam9 * DP1_E2F1_Rbuup_SWI_SNFp / cell)(rateParam3 * DP1_E2F1_Rbppp / cell)(rateParam3 * DP1_E2F1_Rbppu_SWI_SNFu / cell)(rateParam4 * DP1_E2F1_Rbppp / cell)(k * DP1_E2F1_Rbppu_SWI_SNFu / cell)(k * DP1_E2F1_Rbppp * SWI_SNFp / cell)(rateParam11 * HDAC1 * DP1_E2F1_Rbppu_SWI_SNFu / cell)(rateParam2 * DP1_E2F1_Rbupp / cell)(rateParam2 * DP1_E2F1_Rbupu_SWI_SNFu / cell)(rateParam2 * DP1_E2F1_Rbppu / cell)(rateParam2 * DP1_E2F1_Rbppp_SWI_SNFp / cell)(rateParam2 * DP1_E2F1_Rbppu_HDAC1_SWI_SNFu / cell)(rateParam3 * DP1_E2F1_Rbpup / cell)(rateParam3 * DP1_E2F1_Rbpuu_SWI_SNFu / cell)(rateParam3 * DP1_E2F1_Rbppu / cell)(rateParam2 * DP1_E2F1_Rbppp / cell)(rateParam2 * DP1_E2F1_Rbppu_SWI_SNFu / cell)(rateParam3 * DP1_E2F1_Rbppp_SWI_SNFp / cell)(rateParam3 * DP1_E2F1_Rbppu_HDAC1_SWI_SNFu / cell)(rateParam4 * DP1_E2F1_Rbpup / cell)(rateParam4 * DP1_E2F1_Rbupp / cell)(rateParam1 * SWI_SNFp / cell)(rateParam4 * DP1_E2F1_Rbppp_SWI_SNFp / cell)(rateParam5 * DP1_E2F1_Rbuuu * SWI_SNFu / cell)(rateParam5 * SWI_SNFu * DP1_E2F1_Rbppu / cell)(k * DP1_E2F1_Rbpuu_SWI_SNFu / cell)(k * DP1_E2F1_Rbupu_SWI_SNFu / cell)(rateParam6 * DP1_E2F1_Rbppp_SWI_SNFp / cell)(rateParam7 * HDAC1 * DP1_E2F1_Rbpuu_SWI_SNFu / cell)(rateParam9 * DP1_E2F1_Rbppp_SWI_SNFp / cell)(rateParam10 * DP1_E2F1_Rbppu_HDAC1_SWI_SNFu / cell)(rateParam2 * DP1_E2F1_Rbupu / cell)(rateParam2 * DP1_E2F1_Rbupp_SWI_SNFp / cell)(rateParam2 * DP1_E2F1_Rbupu_HDAC1_SWI_SNFu / cell)(rateParam2 * DP1_E2F1_Rbppu_SWI_SNFp / cell)(rateParam3 * DP1_E2F1_Rbpup_SWI_SNFp / cell)(rateParam3 * DP1_E2F1_Rbpuu_HDAC1_SWI_SNFu / cell)(rateParam3 * DP1_E2F1_Rbppu_SWI_SNFp / cell)(rateParam3 * DP1_E2F1_Rbppp_SWI_SNFu / cell)(rateParam4 * DP1_E2F1_Rbuup / cell)(rateParam4 * DP1_E2F1_Rbppp_SWI_SNFu / cell)(rateParam5 * SWI_SNFu * DP1_E2F1_Rbpuu / cell)(rateParam5 * SWI_SNFu * DP1_E2F1_Rbupu / cell)(rateParam2 * DP1_E2F1_Rbppp_SWI_SNFu / cell)(rateParam3 * DP1_E2F1_Rbpuu / cell)(k * DP1_E2F1_Rbuuu_SWI_SNFu / cell)(k * DP1_E2F1_Rbpuu_HDAC1_SWI_SNFu / cell)(rateParam8 * HDAC1 * DP1_E2F1_Rbuuu_SWI_SNFu / cell)(rateParam9 * DP1_E2F1_Rbpup_SWI_SNFp / cell)(rateParam9 * DP1_E2F1_Rbupp_SWI_SNFp / cell)(rateParam9 * DP1_E2F1_Rbppu_SWI_SNFp / cell)(rateParam2 * DP1_E2F1_Rbupu_SWI_SNFp / cell)(rateParam2 * DP1_E2F1_Rbupp_SWI_SNFu / cell)(rateParam4 * DP1_E2F1_Rbpup_SWI_SNFp / cell)(rateParam4 * DP1_E2F1_Rbupp_SWI_SNFp / cell)10.00.010.00.05.00.05.00.00.00.05.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.096480.09.648E-51.0E-96.02E113.1415926535897938314.0300.05.00.00.00.00.00.05.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.00.010.00.11000.00.00166112956810631231.01.05.010.00.0(( - (Size_cell * DP1_E2F1_Rbuuu_HDAC1_SUV39H1_HP1gamma_SWI_SNFu) - (Size_cell * DP1_E2F1_Rbuup_SWI_SNFu) - (Size_cell * DP1_E2F1_Rbuuu_SWI_SNFp) - (Size_cell * DP1_E2F1_Rbupp_SWI_SNFu) - (Size_cell * DP1_E2F1_Rbupu_SWI_SNFp) - (Size_cell * DP1_E2F1_Rbpup_SWI_SNFu) - (Size_cell * DP1_E2F1_Rbpuu_SWI_SNFp) - (Size_cell * DP1_E2F1_Rbuuu_HDAC1_SWI_SNFu) - (Size_cell * DP1_E2F1_Rbuup_SWI_SNFp) - (Size_cell * DP1_E2F1_Rbppp_SWI_SNFu) - (Size_cell * DP1_E2F1_Rbppu_SWI_SNFp) - (Size_cell * DP1_E2F1_Rbupu_HDAC1_SWI_SNFu) - (Size_cell * DP1_E2F1_Rbupp_SWI_SNFp) - (Size_cell * DP1_E2F1_Rbupu) - (Size_cell * DP1_E2F1_Rbpuu_HDAC1_SWI_SNFu) - (Size_cell * DP1_E2F1_Rbpup_SWI_SNFp) - (Size_cell * DP1_E2F1_Rbpuu) - (Size_cell * DP1_E2F1_Rbuuu_SWI_SNFu) - (Size_cell * DP1_E2F1_Rbuup) - (Size_cell * DP1_E2F1_Rbppu_HDAC1_SWI_SNFu) - (Size_cell * DP1_E2F1_Rbppp_SWI_SNFp) - (Size_cell * DP1_E2F1_Rbppu) - (Size_cell * DP1_E2F1_Rbupu_SWI_SNFu) - (Size_cell * DP1_E2F1_Rbupp) - (Size_cell * DP1_E2F1_Rbpuu_SWI_SNFu) - (Size_cell * DP1_E2F1_Rbpup) - (Size_cell * DP1_E2F1_Rbppp) + K_DP1_E2F1_Rbppu_SWI_SNFu_total - (Size_cell * DP1_E2F1_Rbuuu)) / Size_cell)(DP1_E2F1_Rbppu_HDAC1_SWI_SNFu + DP1_E2F1_Rbpuu_HDAC1_SWI_SNFu + DP1_E2F1_Rbupu_HDAC1_SWI_SNFu + DP1_E2F1_Rbuuu_HDAC1_SWI_SNFu + DP1_E2F1_Rbuuu_HDAC1_SUV39H1_HP1gamma_SWI_SNFu)(( - (Size_cell * DP1_E2F1_Rbuuu_HDAC1_SUV39H1_HP1gamma_SWI_SNFu) - (Size_cell * DP1_E2F1_Rbuuu_HDAC1_SWI_SNFu) - (Size_cell * DP1_E2F1_Rbupu_HDAC1_SWI_SNFu) - (Size_cell * DP1_E2F1_Rbpuu_HDAC1_SWI_SNFu) + K_HDAC1_total - (Size_cell * DP1_E2F1_Rbppu_HDAC1_SWI_SNFu)) / Size_cell)(rateParam1 * SWI_SNFp / Size_cell)(rateParam2 * DP1_E2F1_Rbupp / Size_cell)(rateParam2 * DP1_E2F1_Rbupu_SWI_SNFu / Size_cell)(rateParam2 * DP1_E2F1_Rbppu / Size_cell)(rateParam2 * DP1_E2F1_Rbppp_SWI_SNFp / Size_cell)(rateParam2 * DP1_E2F1_Rbppu_HDAC1_SWI_SNFu / Size_cell)(rateParam3 * DP1_E2F1_Rbpup / Size_cell)(rateParam3 * DP1_E2F1_Rbpuu_SWI_SNFu / Size_cell)(rateParam3 * DP1_E2F1_Rbppu / Size_cell)(rateParam3 * DP1_E2F1_Rbppp_SWI_SNFp / Size_cell)(rateParam3 * DP1_E2F1_Rbppu_HDAC1_SWI_SNFu / Size_cell)(rateParam2 * DP1_E2F1_Rbppp / Size_cell)(rateParam4 * DP1_E2F1_Rbpup / Size_cell)(rateParam4 * DP1_E2F1_Rbupp / Size_cell)(rateParam4 * DP1_E2F1_Rbppp_SWI_SNFp / Size_cell)(rateParam5 * DP1_E2F1_Rbuuu * SWI_SNFu / Size_cell)(rateParam5 * SWI_SNFu * DP1_E2F1_Rbppu / Size_cell)(k * DP1_E2F1_Rbpuu_SWI_SNFu / Size_cell)(k * DP1_E2F1_Rbupu_SWI_SNFu / Size_cell)(rateParam6 * DP1_E2F1_Rbppp_SWI_SNFp / Size_cell)(rateParam7 * HDAC1 * DP1_E2F1_Rbpuu_SWI_SNFu / Size_cell)(rateParam9 * DP1_E2F1_Rbppp_SWI_SNFp / Size_cell)(rateParam2 * DP1_E2F1_Rbppu_SWI_SNFu / Size_cell)(rateParam10 * DP1_E2F1_Rbppu_HDAC1_SWI_SNFu / Size_cell)(rateParam2 * DP1_E2F1_Rbupu / Size_cell)(rateParam2 * DP1_E2F1_Rbupp_SWI_SNFp / Size_cell)(rateParam2 * DP1_E2F1_Rbupu_HDAC1_SWI_SNFu / Size_cell)(rateParam2 * DP1_E2F1_Rbppu_SWI_SNFp / Size_cell)(rateParam2 * DP1_E2F1_Rbppp_SWI_SNFu / Size_cell)(rateParam3 * DP1_E2F1_Rbpuu / Size_cell)(rateParam3 * DP1_E2F1_Rbpup_SWI_SNFp / Size_cell)(rateParam3 * DP1_E2F1_Rbpuu_HDAC1_SWI_SNFu / Size_cell)(rateParam3 * DP1_E2F1_Rbppu_SWI_SNFp / Size_cell)(rateParam3 * DP1_E2F1_Rbppp / Size_cell)(rateParam3 * DP1_E2F1_Rbppp_SWI_SNFu / Size_cell)(rateParam4 * DP1_E2F1_Rbuup / Size_cell)(rateParam4 * DP1_E2F1_Rbpup_SWI_SNFp / Size_cell)(rateParam4 * DP1_E2F1_Rbupp_SWI_SNFp / Size_cell)(rateParam4 * DP1_E2F1_Rbppp_SWI_SNFu / Size_cell)(rateParam5 * SWI_SNFu * DP1_E2F1_Rbpuu / Size_cell)(rateParam5 * SWI_SNFu * DP1_E2F1_Rbupu / Size_cell)(k * DP1_E2F1_Rbuuu_SWI_SNFu / Size_cell)(k * DP1_E2F1_Rbpuu_HDAC1_SWI_SNFu / Size_cell)(rateParam8 * HDAC1 * DP1_E2F1_Rbuuu_SWI_SNFu / Size_cell)(rateParam3 * DP1_E2F1_Rbppu_SWI_SNFu / Size_cell)(rateParam9 * DP1_E2F1_Rbpup_SWI_SNFp / Size_cell)(rateParam9 * DP1_E2F1_Rbupp_SWI_SNFp / Size_cell)(rateParam9 * DP1_E2F1_Rbppu_SWI_SNFp / Size_cell)(rateParam2 * DP1_E2F1_Rbupu_SWI_SNFp / Size_cell)(rateParam2 * DP1_E2F1_Rbupp_SWI_SNFu / Size_cell)(rateParam3 * DP1_E2F1_Rbpuu_SWI_SNFp / Size_cell)(rateParam3 * DP1_E2F1_Rbpup_SWI_SNFu / Size_cell)(rateParam4 * DP1_E2F1_Rbuup_SWI_SNFp / Size_cell)(rateParam4 * DP1_E2F1_Rbpup_SWI_SNFu / Size_cell)(rateParam4 * DP1_E2F1_Rbupp_SWI_SNFu / Size_cell)(rateParam4 * DP1_E2F1_Rbppp / Size_cell)(k * DP1_E2F1_Rbuuu_HDAC1_SWI_SNFu / Size_cell)(rateParam9 * DP1_E2F1_Rbuup_SWI_SNFp / Size_cell)(rateParam9 * DP1_E2F1_Rbpuu_SWI_SNFp / Size_cell)(rateParam9 * DP1_E2F1_Rbupu_SWI_SNFp / Size_cell)(rateParam12 * SUV39H1_HP1gamma * DP1_E2F1_Rbuuu_HDAC1_SWI_SNFu / Size_cell)(rateParam4 * DP1_E2F1_Rbuup_SWI_SNFu / Size_cell)(rateParam9 * DP1_E2F1_Rbuuu_SWI_SNFp / Size_cell)(k * DP1_E2F1_Rbuuu_HDAC1_SUV39H1_HP1gamma_SWI_SNFu / Size_cell)(k * DP1_E2F1_Rbppu_SWI_SNFu / Size_cell)(k * DP1_E2F1_Rbppp * SWI_SNFp / Size_cell)(rateParam11 * HDAC1 * DP1_E2F1_Rbppu_SWI_SNFu / Size_cell)((Size_cell * DP1_E2F1_Rbuuu_HDAC1_SUV39H1_HP1gamma_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbuup_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbuuu_SWI_SNFp_init_uM) + (Size_cell * DP1_E2F1_Rbupp_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbupu_SWI_SNFp_init_uM) + (Size_cell * DP1_E2F1_Rbpup_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbpuu_SWI_SNFp_init_uM) + (Size_cell * DP1_E2F1_Rbuuu_HDAC1_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbuup_SWI_SNFp_init_uM) + (Size_cell * DP1_E2F1_Rbppp_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbppu_SWI_SNFp_init_uM) + (Size_cell * DP1_E2F1_Rbupu_HDAC1_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbupp_SWI_SNFp_init_uM) + (Size_cell * DP1_E2F1_Rbupu_init_uM) + (Size_cell * DP1_E2F1_Rbpuu_HDAC1_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbpup_SWI_SNFp_init_uM) + (Size_cell * DP1_E2F1_Rbpuu_init_uM) + (Size_cell * DP1_E2F1_Rbuuu_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbuup_init_uM) + (Size_cell * DP1_E2F1_Rbppu_HDAC1_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbppp_SWI_SNFp_init_uM) + (Size_cell * DP1_E2F1_Rbppu_init_uM) + (Size_cell * DP1_E2F1_Rbupu_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbupp_init_uM) + (Size_cell * DP1_E2F1_Rbpuu_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbpup_init_uM) + (Size_cell * DP1_E2F1_Rbppp_init_uM) + (Size_cell * DP1_E2F1_Rbppu_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbuuu_init_uM))((Size_cell * DP1_E2F1_Rbuuu_HDAC1_SUV39H1_HP1gamma_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbuuu_HDAC1_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbupu_HDAC1_SWI_SNFu_init_uM) + (Size_cell * DP1_E2F1_Rbpuu_HDAC1_SWI_SNFu_init_uM) + (Size_cell * HDAC1_init_uM) + (Size_cell * DP1_E2F1_Rbppu_HDAC1_SWI_SNFu_init_uM))((Size_cell * SUV39H1_HP1gamma_init_uM) + (Size_cell * DP1_E2F1_Rbuuu_HDAC1_SUV39H1_HP1gamma_SWI_SNFu_init_uM))( - (Size_cell * DP1_E2F1_Rbupu_init_uM) - (Size_cell * DP1_E2F1_Rbpuu_init_uM) - (Size_cell * DP1_E2F1_Rbuup_init_uM) - (Size_cell * DP1_E2F1_Rbppu_init_uM) - (Size_cell * DP1_E2F1_Rbupp_init_uM) - (Size_cell * DP1_E2F1_Rbpup_init_uM) + (Size_cell * SWI_SNFu_init_uM) - (Size_cell * DP1_E2F1_Rbppp_init_uM) + (Size_cell * SWI_SNFp_init_uM) - (Size_cell * DP1_E2F1_Rbuuu_init_uM))(0.1 * k)(100.0 * k)(0.1 * k)(10.0 * k)(0.1 * k)(0.1 * k)(0.1 * k)(10.0 * k)(100.0 * k)(10.0 * k)(15.0 * k)((K_SUV39H1_HP1gamma_total - (Size_cell * DP1_E2F1_Rbuuu_HDAC1_SUV39H1_HP1gamma_SWI_SNFu)) / Size_cell)(((Size_cell * DP1_E2F1_Rbupu) + (Size_cell * DP1_E2F1_Rbpuu) + (Size_cell * DP1_E2F1_Rbuup) + (Size_cell * DP1_E2F1_Rbppu) + (Size_cell * DP1_E2F1_Rbupp) + (Size_cell * DP1_E2F1_Rbpup) - (Size_cell * SWI_SNFu) + (Size_cell * DP1_E2F1_Rbppp) + K_SWI_SNFp_total + (Size_cell * DP1_E2F1_Rbuuu)) / Size_cell)(J_R47 + J_R36 + J_R41 - J_R23 + J_R31)DP1_E2F1_Rbuuu_init_uM(J_R27 - J_R2 - J_R8 - J_R4 - J_R6)DP1_E2F1_Rbppp_init_uM(J_R47 - J_R46 - J_R45 + J_R26 + J_R25 - J_R24 - J_R23 + J_R7 + J_R1)SWI_SNFu_init_uM( - J_R20 - J_R15 + J_R2)DP1_E2F1_Rbpup_init_uM(J_R48 + J_R45 - J_R28 - J_R25 + J_R3 - J_R16 + J_R58 + J_R62)DP1_E2F1_Rbpuu_SWI_SNFu_init_uM( - J_R21 + J_R4 - J_R10)DP1_E2F1_Rbupp_init_uM(J_R46 - J_R26 - J_R11 + J_R5 + J_R59 + J_R63)DP1_E2F1_Rbupu_SWI_SNFu_init_uM( - J_R24 - J_R17 - J_R12 + J_R6 + J_R7)DP1_E2F1_Rbppu_init_uM( - J_R29 - J_R27 - J_R22 - J_R18 + J_R8 - J_R13)DP1_E2F1_Rbppp_SWI_SNFp_init_uM( - J_R30 - J_R19 + J_R9 - J_R14)DP1_E2F1_Rbppu_HDAC1_SWI_SNFu_init_uM( - J_R41 + J_R10 + J_R15)DP1_E2F1_Rbuup_init_uM( - J_R49 - J_R47 + J_R23 + J_R16 + J_R11 + J_R60 + J_R65 + J_R66)DP1_E2F1_Rbuuu_SWI_SNFu_init_uM( - J_R36 - J_R45 + J_R25 + J_R12 + J_R20)DP1_E2F1_Rbpuu_init_uM( - J_R42 - J_R50 + J_R13 - J_R37)DP1_E2F1_Rbpup_SWI_SNFp_init_uM( - J_R48 - J_R38 + J_R14 + J_R28)DP1_E2F1_Rbpuu_HDAC1_SWI_SNFu_init_uM( - J_R46 - J_R31 + J_R26 + J_R17 + J_R21)DP1_E2F1_Rbupu_init_uM( - J_R43 - J_R51 + J_R18 - J_R32)DP1_E2F1_Rbupp_SWI_SNFp_init_uM(J_R19 - J_R33)DP1_E2F1_Rbupu_HDAC1_SWI_SNFu_init_uM( - J_R52 - J_R39 + J_R22 - J_R34)DP1_E2F1_Rbppu_SWI_SNFp_init_uM( - J_R35 - J_R44 + J_R29 - J_R40)DP1_E2F1_Rbppp_SWI_SNFu_init_uM(J_R37 + J_R32 - J_R57 - J_R61)DP1_E2F1_Rbuup_SWI_SNFp_init_uM(J_R49 + J_R38 + J_R33 - J_R60 - J_R64 + J_R67)DP1_E2F1_Rbuuu_HDAC1_SWI_SNFu_init_uM(J_R42 + J_R34 - J_R55 - J_R62)DP1_E2F1_Rbpuu_SWI_SNFp_init_uM(J_R50 + J_R35 - J_R56 - J_R58)DP1_E2F1_Rbpup_SWI_SNFu_init_uM(J_R43 - J_R53 - J_R63 + J_R39)DP1_E2F1_Rbupu_SWI_SNFp_init_uM( - J_R54 + J_R51 - J_R59 + J_R40)DP1_E2F1_Rbupp_SWI_SNFu_init_uM(J_R53 - J_R66 + J_R55 + J_R57)DP1_E2F1_Rbuuu_SWI_SNFp_init_uM(J_R54 + J_R61 + J_R56 - J_R65)DP1_E2F1_Rbuup_SWI_SNFu_init_uM(J_R64 - J_R67)DP1_E2F1_Rbuuu_HDAC1_SUV39H1_HP1gamma_SWI_SNFu_init_uM11#Ver 2.6 +begin model +begin parameters + +k 0.1 + +end parameters +begin molecule types # define molecules present in the simulation, Rb has 16 phospho sites + +DP1_E2F1_Rb(Rb1~u~p,Rb2~u~p,Y3~u~p,site1,site2,site3) +HDAC1(site1) +SWI_SNF(site2,P1~u~p) +SUV39H1_HP1gamma(site3) + +end molecule types +begin seed species # initial conditions + +DP1_E2F1_Rb(Rb1~u,Rb2~u,Y3~u,site1,site2,site3) 0 +DP1_E2F1_Rb(Rb1~p,Rb2~p,Y3~p,site1,site2,site3) 5 +HDAC1(site1) 10 +SWI_SNF(site2,P1~p) 10 +DP1_E2F1_Rb(Rb1~p,Rb2~p,Y3~u,site1,site2!2,site3).SWI_SNF(site2!2,P1~u) 5 +SUV39H1_HP1gamma(site3) 5 + +end seed species +begin observables # model outputs + +Molecules FullyAssembl DP1_E2F1_Rb.HDAC1.SWI_SNF + +#Molecules FullyAssembl Cmplx.BW.HD.SU +#Molecules SU_p_inC SU(Y~p).Cmplx +#Molecules Complx_P Cmplx(Y1~p) +#Molecules FullyPhos Cmplx(Y1~p,Y2~p,Y3~p).BW(Y~p).HD(Y~p).SU(Y~p) + +#Molecules Cmpl_p_SU Cmplx(Y1~p).SU +#Molecules Cmpl_u_SU Cmplx(Y1~u).SU + +#Molecules Cmpl_SU Cmplx().SU +#Molecules Cmpl_BW Cmplx().BW + +end observables +begin reaction rules + +SWI_SNF(site2,P1~p)->SWI_SNF(site2,P1~u) 0.1*k +DP1_E2F1_Rb(Rb2~p) -> DP1_E2F1_Rb(Rb2~u) 0.1*k +DP1_E2F1_Rb(Rb1~p) -> DP1_E2F1_Rb(Rb1~u) 0.1*k +DP1_E2F1_Rb(Y3~p) -> DP1_E2F1_Rb(Y3~u) 0.1*k + +#SWI_SNF forms a complex with DP1_E2F1_Rb when DP1_E2F1_Rb Y3 site is unphosphoralated and SWI_SNF is unphospshorylated +DP1_E2F1_Rb(Rb1,Rb2,Y3~u,site1,site2,site3) + SWI_SNF(site2,P1~u) <-> DP1_E2F1_Rb(Rb1,Rb2,Y3~u,site1,site2!2,site3).SWI_SNF(site2!2,P1~u) 10*k,k + +#Complex breaks apart when both Y3 and P1 have phosphates +DP1_E2F1_Rb(Rb1~p,Rb2~p,Y3~p,site1,site2!2,site3).SWI_SNF(site2!2,P1~p) <-> DP1_E2F1_Rb(Rb1~p,Rb2~p,Y3~p,site1,site2,site3) + SWI_SNF(site2,P1~p) 100*k,k + +#HDAC1 stuff: Binds DP1_E2F1_Rb.SWI_SNF only if it has one phosphate or zero phosphates. I presume that zero will have a higher afinity than one +DP1_E2F1_Rb(Rb1~p,Rb2~u,Y3~u,site1,site2!2,site3).SWI_SNF(site2!2,P1~u) + HDAC1(site1) <-> DP1_E2F1_Rb(Rb1~p,Rb2~u,Y3~u,site1!1,site2!2,site3).SWI_SNF(site2!2,P1~u).HDAC1(site1!1) 10*k,k + +#DP1_E2F1_Rb.SWI_SNF.HDAC forms with zero phosphates +DP1_E2F1_Rb(Rb1~u,Rb2~u,Y3~u,site1,site2!2,site3).SWI_SNF(site2!2,P1~u) + HDAC1(site1) <-> DP1_E2F1_Rb(Rb1~u,Rb2~u,Y3~u,site1!1,site2!2,site3).SWI_SNF(site2!2,P1~u).HDAC1(site1!1) 15*k,k + +#DP1_E2F1_Rb???.SWI_SNFp dephosphorolates when in complex with DP1_E2F1_Rb at a rate independant DP1_E2F1_Rb state +#This models a background phosatase effect +DP1_E2F1_Rb(site1,site2!2,site3).SWI_SNF(site2!2,P1~p) -> DP1_E2F1_Rb(site1,site2!2,site3).SWI_SNF(site2!2,P1~u) + +#HDAC dissassociates from DP1_E2F1_Rb.SWI_SNF.HDAC with 2 phospates +DP1_E2F1_Rb(Rb1~p,Rb2~p,Y3~u,site1!1,site2!2,site3).SWI_SNF(site2!2,P1~u).HDAC1(site1!1) <-> DP1_E2F1_Rb(Rb1~p,Rb2~p,Y3~u,site1,site2!2,site3).SWI_SNF(site2!2,P1~u) + HDAC1(site1) 100*k,0.1*k + +#HP1gamma stuff HP1gamma is associated with gene CBX3 (binds the nuclear lamin). It joins the DP1_E2F1_Rb.SWI_SNF.HDAC with the Histone Methyl transferase (SUV(3-9)h1) as a complex but only if it is not phosporolated + DP1_E2F1_Rb(Rb1~u,Rb2~u,Y3~u,site1!1,site2!2,site3).SWI_SNF(site2!2,P1~u).HDAC1(site1!1) + SUV39H1_HP1gamma(site3) <-> DP1_E2F1_Rb(Rb1~u,Rb2~u,Y3~u,site1!1,site2!2,site3!3).SWI_SNF(site2!2,P1~u).HDAC1(site1!1).SUV39H1_HP1gamma(site3!3) 10*k,k + +#So together DP1_E2F1_Rb(Rb1~u,Rb2~u,Y3~u,site1!1,site2!2,site3!3).SWI_SNF(site2!2,P1~u).HDAC1(site1!1).SUV39H1_HP1gamma(site3!3) interact with Dna and the chromatin. Next is to work on genes and histones + +end reaction rules +end model + +## model ACTIONS + +# generate network of all species and reactions +# with restrictions on iterations and complex size (aggregation) +generate_network({overwrite=>1,max_iter=>12,max_agg=>12}); +writeSBML(); # Output file as SBML. +#simulate_ode({suffix=>ode,t_start=>0,t_end=>1,n_steps=>120}); + +#%VC% speciesRenamePattern("\." , "_") #replace . with _ +#%VC% speciesRenamePattern("[\(,][a-zA-Z]\w*", "") #remove any text after ( or , +#%VC% speciesRenamePattern("~|!\d*", "") #remove ~ or ! and any digit after that +#%VC% speciesRenamePattern("\(", "") #remove ( + +#%VC% speciesRenamePattern("\)", "") # remove )