%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
%%
%% Simulation of early meiotic assembly in mouse occytes
%% Configuration file
%% From Letort et al., 2018
%%
%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%


set simul centrosome
{
	time_step = 0.02      %  
	kT = 0.0042            % 25 C
    viscosity = 1  	       % Kimura and Onami 2010, Kole 2005 Mol.Biol.Cell (0.13-0.46)
    steric = 1, 15, 1.5    % crosslinkers in spindle, crowding agents and steric interactions (Groen 2011)
	verbose = 0
}

set space cell
{
   geometry = (circle 20)
}

new space cell

%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
%% MTs
set fiber mt
{		
	rigidity = 30                 
	segmentation = 0.5 
	activity = classic 
	growing_speed = 0.6            
	growing_force = 5
	catastrophe_rate = 0.08, 0.08
    shrinking_speed = -0.6
	catastrophe_length = 5  
	min_length = 0.05
	max_length = 10
	binding_key = 1
    steric = 1, 0.025, 0.025		 %% Loughlin 2010
	ran_distance = -1
	ran_growth = 1 
	ran_stabilization = 0.1;
	ran_name	= "dna";
}

%-------------------------------------------------
%% Kinesin 5, motors pushing MTs, parameters from Loughlin 2010
set hand kin_motor
{
	binding_rate = 3
    binding_range = 0.07
    unbinding_rate = 0.05
    unbinding_force = 5
	binding_key = 1
	activity = move
	max_speed = 0.04   
	stall_force = 5 
	hold_growing_end = 1
	hold_shrinking_end = 0
	hold_minus_shrinking_end = 1  
}

set couple kinesinLater
{
	hand1 = kin_motor
	hand2 = kin_motor
	stiffness = 100 
	activity = crosslink
	length = 0.05
	diffusion = 30
	fast_diffusion = 1
	production_rate = 0.0005
}

%% HSET == kinesin 14, towards minus
set hand hset_bind
{
	binding_rate = 3
    binding_range = 0.07
    unbinding_rate = 0.05
    unbinding_force = 5
	hold_growing_end = 1  
	hold_minus_shrinking_end = 1  
	binding_key = 1
}

set hand hset_motor
{
	binding_rate = 15     %% Braun et aL, 2017, very fast binding on overlaps
    binding_range = 0.07
    unbinding_rate = 1   %% Braun et al., 2017, very fast unbinding (4 s^-1)
    unbinding_force = 5
	binding_key = 1
	activity = move
	max_speed = -0.15	%% Norris et al 2018: (Fink et al. 2009, Ncd)    
	stall_force = 5 
	hold_growing_end = 1  
	hold_minus_shrinking_end = 1  
    display = { visible = 0; }
}

set couple hset
{
	hand1 = hset_bind
	hand2 = hset_motor
	stiffness = 100 
	activity = crosslink
	trans_activated = 1   %% Braun et al. 2017, bind 6* + to overlaps than singles, and mainly tail
	diffusion = 30
	fast_diffusion = 1
	length = 0.05
}

%% NuMA, crosslinks minus end together
%% C-terminal, bind close to MT minus end Hueschen et al., 2017
%% depolym effect of MCAK/Kif2a
set hand numah
{
	binding_rate = 3
    binding_range = 0.1
    unbinding_rate = 0.05 
    unbinding_force = 5
	bind_end = minus_end, 0.25
	activity = track
	track_end = minus_end
	hold_growing_end = 1
	hold_shrinking_end = 1  
	hold_minus_shrinking_end = 1  
	chewing_rate = 0.01%6  %% Hunter et al 2003
}

%% N-termainl, recruits dynein/dynactin complex, Hueschen et al., 2017
set hand dynh
{
	binding_rate = 3
    binding_range = 0.1
    unbinding_rate = 0.05 
    unbinding_force = 5
	bind_end = minus_end, 0.5
	activity = move
	max_speed = -1
	stall_force = 5
	hold_growing_end = 1
	hold_shrinking_end = 1  
	hold_minus_shrinking_end = 1  
}

set couple numa
{
	hand1 = numah
	hand2 = dynh
	stiffness = 100 
	activity = crosslink
	%specificity = parallel
	length = 0.1
	fast_diffusion = 1
	%production_rate = 0.005 
}


set hand hurp_bind
{
	binding_rate = 7
    binding_range = 0.07
    unbinding_rate = 1
    unbinding_force = 5
	hold_growing_end = 1  
	hold_minus_shrinking_end = 1  
	binding_key = 1
	stabilize = 1
	activity = move
	max_speed = 0.5
	fixed_loaded = 1
	stall_force = 5
}

set couple hurpLater
{
	hand1 = hurp_bind
	hand2 = hurp_bind
	activity = ran
	activation_by = dna
	activation_range = 1
	deactivation_rate = 0.5
	specificity = antiparallel
	stiffness = 100
	diffusion = 20
	active_diffusion = 1
	production_rate = 0.005 
}

%-------------------------------------------------
%% Nucleation: activated in central zone, Ran gradient and augmin
set hand nuch
{
	activity = nucleate
	nucleate = 0.5, mt, {length = 0.01; end_state = 1, 0}
	display = { visible=0; }
	specificity = parallel_if
	hold_end = minus_end
	track_end = minus_end
	hold_growing_end = 1  
	hold_shrinking_end = 1  
	hold_minus_shrinking_end = 1  
}

set hand bindh
{
	binding_rate = 0 % 0.5
	unbinding_rate = 0.1
	binding_range = 0.06
	unbinding_force = 5
	binding_key = 1
	activity = move
	max_speed = -1
	stall_force = 3
	hold_shrinking_end = 0
	hold_minus_shrinking_end = 1  
	hold_growing_end = 1
	fixed_loaded = 1
}

set couple nucleator
{
	hand1 = nuch
	hand2 = bindh
	stiffness = 100
	diffusion = 10
	active_diffusion = 1
	activity = ran
	activation_by = dna
	activation_range = 1 
    deactivation_rate = 0.5
	trans_activated = 2 %% hand2 doesn'ti bind when hand1 has nucleated
	length = 0.05
}

%% DNA
set sphere dna
{
	point_mobility = 0.01
	viscosity = 20  
    steric = 1	
    display        = { style=1; color="blue"; }
}

%% repulsing
set hand reph
{
	binding_rate = 5
    binding_range = 0.08 
    unbinding_rate = 0.1 
    unbinding_force = 5
	bind_only_end = plus_end, 0.25 
	hold_growing_end = 1
	binding_key = 1
}

set single repul
{
	hand = reph
	stiffness = 100
}

%% AMTOC 
set solid mtoc
{
	viscosity = 150
    display = { style=5; color = "grey"; }
}

set aster amtoc
{
  solid = mtoc
  fibers = mt
  stiffness = 500, 0
  nucleation_rate = 0.05 
  nucleation_spec = (end_state = 1, 0)
}

%--------------------------------------------------------------------------------------------
%% Simu

new 10 sphere dna
{
	position = disc 4
	radius = 0.5
	point1 = 50, surface
	attach = 1 repul each
}

new 15 aster amtoc
{ 
	position = circle 8 3
	length = 0.5, 0.1
	end_state = 4, 0
    radius = 0.25
    nb_fibers = 10
}

new 800 couple nucleator

new 1000 couple hset
new 2500 couple numa

new 2000 couple hurpLater
new 1000 couple kinesinLater

run simul *
{
	nb_steps = 45000 
    nb_frames = 200
}