###################################################################### # Gillespie simulation of late LTP # # Author: Peter Helfer # Date: 2016-11-07 # ###################################################################### # Reaction constants # # name value define: r_phos_kf 10 # R phosphorylation by PKMZ (forward) define: r_phos_kr 400 # R phosphorylation by PKMZ (reverse) define: r_phos_kc 100 # R phosphorylation by PKMZ (catalytic) define: e1_r_phos_kf 10 # R phosphorylation by E1_A (forward) define: e1_r_phos_kr 400 # R phosphorylation by E1_A (reverse) define: e1_r_phos_kc 100 # R phosphorylation by E1_A (catalytic) define: r_deph_kf 4 # R dephosphorylation (forward) define: r_deph_kr 400 # R dephosphorylation (reverse) define: r_deph_kc 100 # R dephosphorylation (catalytic) define: b_phos_kf 1 # BRAG phosphorylation (forward) define: b_phos_kr 400 # BRAG phosphorylation (reverse) define: b_phos_kc 20 # BRAG phosphorylation (catalytic) define: b_deph_kf 1 # BRAG dephosphorylation (forward) define: b_deph_kr 400 # BRAG dephosphorylation (reverse) define: b_deph_kc 0.06 # BRAG dephosphorylation (catalytic) define: a_endo_kf 10 # catalyzed AMPAR endocytosis (forward) define: a_endo_kr 400 # catalyzed AMPAR endocytosis (reverse) define: a_endo_kc 4 # catalyzed AMPAR endocytosis (catalytic) define: a_exo_kf 0.4 # catalyzed AMPAR insertion (forward) define: a_exo_kr 400 # catalyzed AMPAR insertion (reverse) define: a_exo_kc 20 # catalyzed AMPAR insertion (catalytic) define: p_degr 0.65 # PKMZ degradation when not bound to A_I define: p_ai_degr 0.0001 # PKMZ degradation when bound to A_I # Containment volume # volume: 1.0 idletick: 0.1 ###################################################################### # Molecules # id count description # molecule: P 0 "Unbound PKMZ" molecule: R_I 100 "unphosphorylated PKMZ mRNA (inactive)" molecule: R_A 0 "phosphorylated PKMZ mRNA (active)" molecule: PP 100 "phosphatase" molecule: PP.R_A 0 "PP + R_A complex" molecule: E1_A 0 "stimulation enzyme, active" molecule: E1_I 100 "stimulation enzyme, inactive" molecule: E1_A.R_I 0 "E1_A + R_I complex" molecule: A_U 100 "Uninserted GluR2 AMPAR" molecule: A_I 0 "Inserted GluR2 AMPAR" molecule: A_I.P 0 "PKMZ bound to inserted AMPAR" molecule: A_U.P 0 "PKMZ bound to uninserted AMPAR" molecule: P.R_I 0 "P + R_I complex" molecule: A_I.P.R_I 0 "A_I + P + R_I complex" molecule: B_A 100 "Active BRAG1" molecule: B_I 0 "Inactive BRAG1" molecule: PP.B_I 0 "PP + B_I complex" molecule: P.B_A 0 "P + B_A complex" molecule: A_I.P.B_A 0 "A_I + P + B_A complex" molecule: B_A.A_I 0 "B_A + A_I complex" molecule: B_A.A_I.P 0 "B_A + A_I + P complex" molecule: E2_A 0 "reactivation enzyme, active" molecule: E2_I 100 "reactivation enzyme, inactive" ###################################################################### # Reactions # id formula k description # in paper # mRNA activation reaction: p_ph_ri "P + R_I ---> P.R_I" r_phos_kf "Formation of P.R_I complex" # 1 - reaction: r* "P.R_I ---> P + R_I" r_phos_kr "Dissolution of P.R_I complex" # 2 - reaction: r* "P.R_I ---> P + R_A" r_phos_kc "R_I phosphorylation" # 3 - # mRNA deactivation reaction: r* "PP + R_A ---> PP.R_A" r_deph_kf "Formation of PP + R_A complex" # 4 - reaction: r* "PP.R_A ---> PP + R_A" r_deph_kr "Dissolution of PP.R_A complex" # 5 - reaction: r* "PP.R_A ---> PP + R_I" r_deph_kc "R_A dephosphorylation" # 6 - # PKMZ synthesis/degradation reaction: psynth "R_A ---> R_A + P" 0.20 "PKMZ synthesis" # 7 - reaction: pdegr "P ---> 0" p_degr "Degradation of free PKMZ" # 8 - # BRAG2 deactivation reaction: p_ph_ba "P + B_A ---> P.B_A" b_phos_kf "Formation of P.B_A complex" # 9 - reaction: r* "P.B_A ---> P + B_A" b_phos_kr "Dissolution of P.B_A complex" # 10 - reaction: r* "P.B_A ---> P + B_I" b_phos_kc "R_A phosphorylation" # 11 - # BRAG1 activation reaction: r* "PP + B_I ---> PP.B_I" b_deph_kf "Formation of PP + B_I complex" # 12 - reaction: r* "PP.B_I ---> PP + B_I" b_deph_kr "Dissolution of PP.B_I complex" # 13 - reaction: r* "PP.B_I ---> PP + B_A" b_deph_kc "BRAG1 dephosphorylation" # 14 - # PKMZ-catalyzed AMPAR trafficking into PSD reaction: p-au-ai "P + A_U ---> A_U.P" a_exo_kf "Formation of P.A_U complex" # 15 - reaction: r* "A_U.P ---> P + A_U" a_exo_kr "Dissolution of A_U.P complex" # 16 - reaction: r* "A_U.P ---> P + A_I" a_exo_kc "P-catalyzed AMPAR insertion" # 17 - reaction: r* "A_U.P ---> A_U" p_degr "Degradation of PKMZ bound to A_U" # # BRAG2-catalyzed AMPAR endocytosis reaction: ba-ai-au "B_A + A_I ---> B_A.A_I" a_endo_kf "Formation of B_A.A_I complex" # 18 - reaction: r* "B_A.A_I ---> B_A + A_I" a_endo_kr "Dissolution of B_A.A_I complex" # 19 - reaction: r* "B_A.A_I ---> B_A + A_U" a_endo_kc "BRAG-catalyzed AMPAR endocytosis" # 20 - # Constitutive AMPAR trafficking reaction: r* "A_U ---> A_I" 0.05 "Basal AMPAR exocytosis" # 21 - reaction: r* "A_I ---> A_U" 0.005 "spontaneous AMPAR endocytosis" # 22 - # PKMZ binding to/detaching from AMPAR reaction: r* "P + A_I ---> A_I.P" 1.0 "Inserted AMPAR binds PKMZ" # 23 - reaction: r* "A_I.P ---> A_I" p_ai_degr "Degradation of PKMZ bound to A_I" # 24 - # BRAG2-catalyzed endocytosis of AMPAR with attached PKMZ reaction: ba-aip-au "B_A + A_I.P ---> B_A.A_I.P" a_endo_kf "Formation of B_A.A_I.P complex" # 25 - reaction: r* "B_A.A_I.P ---> B_A + A_I.P" a_endo_kr "Dissolution of B_A.A_I.P complex" # 26 - reaction: r* "B_A.A_I.P ---> B_A + A_U + P" a_endo_kc "BRAG-catalyzed AMPAR endocytosis" # 27 - # Constitutive endocytosis of AMPAR with attached PKMZ reaction: r* "A_I.P ---> A_U + P" 0.005 "spontaneous AMPAR endocytosis" # 28 - # mRNA activation catalyzed by PKMZ bound to AMPAR reaction: aip_ph_ri "A_I.P + R_I ---> A_I.P.R_I" r_phos_kf "Formation of A_I.P.R_I complex" # 29 - reaction: r* "A_I.P.R_I ---> A_I.P + R_I" r_phos_kr "Dissolution of A_I.P.R_I complex" # 30 - reaction: r* "A_I.P.R_I ---> A_I.P + R_A" r_phos_kc "R_I phosphorylation" # 31 - # BRAG2 deactivation catalyzed by PKMZ bound to AMPAR reaction: aip_ph_ba "A_I.P + B_A ---> A_I.P.B_A" b_phos_kf "Formation of A_I.P.B_A complex" # 32 - reaction: r* "A_I.P.B_A ---> A_I.P + B_A" b_phos_kr "Dissolution of A_I.P.B_A complex" # 33 - reaction: r* "A_I.P.B_A ---> A_I.P + B_I" b_phos_kc "R_A phosphorylation" # 34 - # Reactions catalyzed by NMDAR-stimulation-activated enzyme E1 reaction: e1_ph_ri "E1_A + R_I ---> E1_A.R_I" e1_r_phos_kf "Formation of E1_A.R_I complex" # 35 - reaction: r* "E1_A.R_I ---> E1_A + R_I" e1_r_phos_kr "Dissolution of E1_A.R_I complex" # 36 - reaction: r* "E1_A.R_I ---> E1_A + R_A" e1_r_phos_kc "R_I phosphorylation" # 37 - # Deactivation of NMDAR-stimulation-activated enzyme E1 reaction: r* "E1_A ---> E1_I" 0.3 "E1_A deactivation" # 38 - # Reactions catalyzed by reactivation-activated enzyme E2 reaction: e2a-ai-au "E2_A + A_I ---> E2_A + A_U" 0.1 "E2_A-catalyzed AMPAR endocytosis" # 39 - reaction: e2a-aip-au "E2_A + A_I.P ---> E2_A + A_U + P" 0.1 "E2_A-catalyzed AMPAR endocytosis" # 40 - reaction: r* "E2_A ---> E2_I" 0.5 "E2_A deactivation" # 41 -