Isotypes
In FiberSim, myosin and myosin binding protein-C molecules have an isotype.
Different isotypes follow different kinetic schemes. You can also define the proportion of molecules that have each isotype. This framework provides a lot of flexibility. Examples of things it allows you to simulate include:
- changing the relative expression of alpha and beta myosin heavy chain
- phosphorylating a proportion of myosin binding protein-C molecules
- dose-response curves for myotropes
The isotypes in these three examples correspond to:
- different myosin isoforms
- MyBP-C molecules with different phosphorylation statuses
- myosins with/without a drug bound
Model files
Isotypes are defined via the model file. Here is the relevant section of a file that defines two myosin isotypes.
"m_parameters": {
"m_k_cb": 0.001,
"m_isotype_proportions": [ 0.7, 0.3 ]
},
"m_kinetics": [
{
"state":
[
{
"number": 1,
"type": "S",
"extension": 0,
"transition": [
{
"new_state": 2,
"rate_type": "force_dependent",
"rate_parameters": [ 20, 200]
}
]
},
{
"number": 2,
"type": "D",
"extension": 0,
"transition": [
{
"new_state": 1,
"rate_type": "constant",
"rate_parameters": [ 100 ]
},
{
"new_state": 3,
"rate_type": "gaussian_hsl",
"rate_parameters": [ 50 ]
}
]
},
{
"number": 3,
"type": "A",
"extension": 5.0,
"transition": [
{
"new_state": 2,
"rate_type": "exp_wall",
"rate_parameters": [ 150, 2, 4, 7]
}
]
}
]
},
{
"state":
[
{
"number": 1,
"type": "S",
"extension": 0,
"transition": [
{
"new_state": 2,
"rate_type": "force_dependent",
"rate_parameters": [ 40, 400]
}
]
},
{
"number": 2,
"type": "D",
"extension": 0,
"transition": [
{
"new_state": 1,
"rate_type": "constant",
"rate_parameters": [ 100 ]
},
{
"new_state": 3,
"rate_type": "gaussian_hsl",
"rate_parameters": [ 100 ]
}
]
},
{
"number": 3,
"type": "A",
"extension": 5.0,
"transition": [
{
"new_state": 2,
"rate_type": "exp_wall",
"rate_parameters": [ 300, 2, 4, 7]
}
]
}
]
}
]
The third line of the snippet is
"m_isotype_proportions": [ 0.7, 0.3 ]
This tells FiberSim that there are two isotypes. 70% of the myosins should be the first isotype. The remaining 30% will be the second isotype.
If you are used to looking at JSON files, you will realize that the next section which starts
"m_kinetics: [
{
<SNIP>
}
]
is defining an array. Each element of the array (there are two) is a complete scheme, containing different states (in this case 3) and different transitions.
The structure might be easier to understand if you look at the image rendered by JSON Crack.
The first scheme corresponds to the first isotype, the second scheme to the second isotype.
If you run a simulation based on this model file, 70% of the myosins will follow the first kinetic scheme, and 30% will follow the second.
Check the examples for further explanations and tips.