- Author:
- Shelley Fong <s.fong@auckland.ac.nz>
- Date:
- 2021-11-10 14:40:25+13:00
- Desc:
- Fixing exposure files
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/705/rawfile/2fe62170795cead474fd15120998d64bb1d6e493/parameter_finder/grand_kinetic_parameters.m
% Kinetic rate constants for composite model of FCU-AC
% they must be computed together because of the presence of new potential closed loops
% order: {'cAMP','LRGbinding_B1AR','LRGbinding_M2','GsProtein','GiProtein'}
function [k_kinetic, N_cT, K_C, W] = grand_kinetic_parameters(M, include_type2_reactions, dims, V, noLRG)
num_cols = dims.num_cols;
num_rows = dims.num_rows;
% shared large/small constants
bigNum = 1e5;
fastKineticConstant = bigNum;
smallReverse = 1e0;
% cAMP
K1_m = 1.03e3; % uM
k1cat = 0.2; % 1/s
K2_m = 3.15e+2; % uM
k2cat = 8.5; % 1/s
K3_m = 8.60e+2; % uM
k3cat = 1e-16; % 1/s
K4_m = 1.30; % uM
k4cat = 5; % 1/s
K5_m = 30; % uM
K6_m = 0.4; % uM
K7_m = 44; % uM
KGiAC_m = 10; % made up value % uM
% initialise arrays
vkap = zeros(4,1);
vkam = zeros(4,1);
vkbp = zeros(4,1);
vkbm = zeros(4,1);
vkm2 = zeros(4,1);
vkp2 = zeros(4,1);
vK_m = [K1_m,K2_m,K3_m,K4_m,K5_m,K6_m,K7_m,KGiAC_m];
vkcat = [k1cat,k2cat,k3cat,k4cat];
kap_mult = [0.93, 0.1, 1, 1,0.1]; % finding rates from literature?
% include the Gi reaction to remove it from the system in inhibited
% form
iks = 1:4;
for i=1:4
vkap(i) = kap_mult(i)*fastKineticConstant;
vkam(i) = vkap(i)*vK_m(iks(i)) - vkcat(i);
vkbp(i) = vkcat(i);
vkbm(i) = (vkap(i)*vkbp(i))/vkam(i);
end
iks = 5:8;
for i= 1:4
vkm2(i) = fastKineticConstant;
vkp2(i) = vkm2(i)/vK_m(iks(i));
end
% B1AR composite: LRG_B1AR + GsProtein
kPhosRGp = fastKineticConstant;
kPhosRGm = fastKineticConstant;
kPhosLRGp = fastKineticConstant;
kPhosLRGm = fastKineticConstant;
Ksig1 = 33; % uM Kc
Ksig2 = 0.285; % uM Kl
Ksig3 = 0.062; % uM Kr
ksig1p = fastKineticConstant;
ksig1m = ksig1p*Ksig1;
ksig2p = fastKineticConstant;
ksig2m = ksig2p*Ksig2;
ksig3p = fastKineticConstant;
ksig3m = ksig3p*Ksig3;
ksig4p = fastKineticConstant;
% find ksig4m using detailed balance
ksig4m = ksig1m*ksig2m*ksig3p*ksig4p/(ksig1p*ksig2p*ksig3m);
kAct1p = 16; % 1/s
kAct1m = smallReverse; % 1/s
kAct2p = 16; % 1/s
kAct2m = smallReverse; % 1/s
kHydp = 0.8; % 1/s
kHydm = smallReverse; % 1/s
kReassocp = 1.21e3; % 1/uM.s
kReassocm = kReassocp/fastKineticConstant; % 1/s
% Loop1: find kact1m using detailed balance
kAct1m = (kAct1p*ksig1p)/ksig1m;
% Loop2: find kact1m using detailed balance
kAct2m = (kAct2p*ksig3p)/ksig3m;
% Big Loop: find ksig3p or kact2m using detailed balance
% *** unnecessary ***
ksig3m = kAct1p*ksig2m*ksig3p*ksig4p/(kAct1m*ksig2p*ksig4m);
% CLOSED LOOP involving G - aGTP - aGDP - G
% use detailed balance to find kReasocm with either Act (as they have
% same equilibrium constant
if true
kReassocm = kAct1p*kHydp*kReassocp/(kAct1m*kHydm);
end
% M2 composite: LRG_M2 + GiProtein
K_M2sig1 = 30; % uM Kc
K_M2sig2 = 0.16; % uM Kh
K_M2sig4 = 11; % uM Kl
k_M2sig1p = fastKineticConstant;
k_M2sig1m = k_M2sig1p*K_M2sig1;
k_M2sig2p = fastKineticConstant;
k_M2sig2m = k_M2sig2p*K_M2sig2;
k_M2sig4p = fastKineticConstant;
k_M2sig4m = k_M2sig4p*K_M2sig4;
k_M2sig3p = fastKineticConstant;
k_M2sig3m = k_M2sig1m*k_M2sig2m*k_M2sig3p*k_M2sig4p/(k_M2sig1p*k_M2sig2p*k_M2sig4m); % interim?
k_M2PhosRGp = fastKineticConstant;
k_M2PhosRGm = fastKineticConstant;
k_M2PhosLRGp = fastKineticConstant;
k_M2PhosLRGm = fastKineticConstant;
k_M2Act1p = 2.5; % 1/s
k_M2Act1m = smallReverse; % 1/s
k_M2Act2p = 0.05; % 1/s
k_M2Act2m = smallReverse; % 1/s
k_M2Hydp = 0.8; % 1/s
k_M2Hydm = smallReverse; % 1/s
k_M2Reassocp = 1.21e3; % 1/uM.s
k_M2Reassocm = k_M2Reassocp/fastKineticConstant; % 1/s
% Loop1: find kact1m using detailed balance
k_M2Act1m = (k_M2Act1p*k_M2sig1p)/k_M2sig1m;
% Loop2: find kact1m using detailed balance
k_M2Act2m = (k_M2Act2p*k_M2sig3p)/k_M2sig3m;
% Big Loop: find k_M2sig3p or kact2m using detailed balance
% *** unnecessary ***
k_M2sig3m = k_M2Act1p*k_M2sig2m*k_M2sig3p*k_M2sig4p/(k_M2Act1m*k_M2sig2p*k_M2sig4m);
% CLOSED LOOP involving G - aGTP - aGDP - G
% use detailed balance to find kReasocm with either Act (as they have
% same equilibrium constant
if true
k_M2Reassocm = k_M2Act1p*k_M2Hydp*k_M2Reassocp/(k_M2Act1m*k_M2Hydm);
end
% TOTAL
% order: {'cAMP','LRGbinding_B1AR','LRGbinding_M2','GsProtein','GiProtein'}
% forwaard first, then reverse!
k_kinetic = [vkap(1) vkbp(1) ... %cAMP
vkap(2) vkbp(2) ...
vkap(3) vkbp(3) ...
vkap(4) vkbp(4) ...
vkp2(1:4)' ...
ksig1p, ksig2p, ksig3p, ksig4p... %LRG B1AR
k_M2sig1p, k_M2sig2p, k_M2sig3p, k_M2sig4p...% LRG_M2
kPhosRGp, kPhosLRGp, kAct1p, kAct2p, kHydp, kReassocp... %GsProtein
k_M2PhosRGp, k_M2PhosLRGp, k_M2Act1p, k_M2Act2p, k_M2Hydp, k_M2Reassocp... %GiProtein
vkam(1) vkbm(1) ...
vkam(2) vkbm(2) ...
vkam(3) vkbm(3) ...
vkam(4) vkbm(4) ...
vkm2(1:4)'...
ksig1m, ksig2m, ksig3m, ksig4m...
k_M2sig1m, k_M2sig2m, k_M2sig3m, k_M2sig4m...
kPhosRGm, kPhosLRGm, kAct1m, kAct2m, kHydm, kReassocm...
k_M2PhosRGm, k_M2PhosLRGm, k_M2Act1m, k_M2Act2m, k_M2Hydm, k_M2Reassocm
]';
if noLRG
k_kinetic = [vkap(1) vkbp(1) ... %cAMP
vkap(2) vkbp(2) ...
vkap(3) vkbp(3) ...
vkap(4) vkbp(4) ...
vkp2(1:4)' ...
kPhosRGp, kPhosLRGp, kAct1p, kAct2p, kHydp, kReassocp... %GsProtein
k_M2PhosRGp, k_M2PhosLRGp, k_M2Act1p, k_M2Act2p, k_M2Hydp, k_M2Reassocp... %GiProtein
vkam(1) vkbm(1) ...
vkam(2) vkbm(2) ...
vkam(3) vkbm(3) ...
vkam(4) vkbm(4) ...
vkm2(1:4)'...
kPhosRGm, kPhosLRGm, kAct1m, kAct2m, kHydm, kReassocm...
k_M2PhosRGm, k_M2PhosLRGm, k_M2Act1m, k_M2Act2m, k_M2Hydm, k_M2Reassocm
]';
end
if false % Gs and LRG_B1 only
k_kinetic = [ksig1p, ksig2p, ksig3p, ksig4p... %LRG B1AR
kAct1p, kAct2p, kHydp, kReassocp... %GsProtein
ksig1m, ksig2m, ksig3m, ksig4m...
kAct1m, kAct2m, kHydm, kReassocm...
]';
end
if false
k_kinetic = [k_M2sig1p, k_M2sig2p, k_M2sig3p, k_M2sig4p...% LRG_M2
k_M2Act1p, k_M2Act2p, k_M2Hydp, k_M2Reassocp... %GiProtein
k_M2sig1m, k_M2sig2m, k_M2sig3m, k_M2sig4m...
k_M2Act1m, k_M2Act2m, k_M2Hydm, k_M2Reassocm
]';
end
% CONSTRAINTS
N_cT = [];
if false
N_cT = zeros(1,size(M,2));
% substrate B1ARp is in eqlm with product B1ARtot
N_cT(1,num_cols + 1) = 1;
N_cT(1,num_cols + 2) = -1;
end
K_C = ones(1,size(N_cT,1));
% volume vector
W = [ones(num_cols,1); V.V_myo*ones(num_rows,1)];
return
