Difference between revisions of "Team:HokkaidoU Japan/Model"
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<span class="nomal2"> | <span class="nomal2"> | ||
| − | <br>To think about the power of stabilization by | + | <br>In our project, we tried to stabilize protein structure |
| + | by circularization using SAPs. About the detailed concept of | ||
| + | circularization, please read <a href="https://2016.igem.org/Team:HokkaidoU_Japan/Circularization">circularization page</a>. To think about the power | ||
| + | of stabilization by | ||
circularization using SAPs, we used HP (Hydrophobic-Polar) model. | circularization using SAPs, we used HP (Hydrophobic-Polar) model. | ||
HP model is a kind of simplified protein folding model and in this model, | HP model is a kind of simplified protein folding model and in this model, | ||
Revision as of 13:57, 19 October 2016
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In our project, we tried to stabilize protein structure by circularization using SAPs. About the detailed concept of circularization, please read circularization page. To think about the power of stabilization by circularization using SAPs, we used HP (Hydrophobic-Polar) model. HP model is a kind of simplified protein folding model and in this model, protein chain is given as zig-zag stick on 2D lattice. Each residue has the characteristic H or P (Hydrophobic or Polar). To calculate the stability of protein structures, in this model, if an H residue is next to another H residue without covalent bond, it decreases free energy because of hydrophobic interaction. In our model, the decreased energy by each hydrophobic interaction is defined as -EH. We added another characteristic SAP into this model. Through thinking about this model, we can simply think about the effect of SAPs reflected as the effect to probability to fold as native state. We thought SAPs interaction is so strong, so in the case we add SAPs at N terminus and C terminus, both ends are set next to each other in the model. So, let's think about the simplest model.
The simplest model is the model with the number of residue is 4 and the sequence is HPPH. In this case, without SAPs, the number of states is 4, excluding enantiomers and rotamers. The possible states and the energy are listed below. KB is Boltzmann constant 1.38064852*10-23 (J/K), T is temperature (K).
Only the first one is stable and its energy is -EH. Because it's most stable, we thought it's native state. The probability to fold as native state (PHPPH) is below.
To calculate this, we used canonical ensemble from statistical mechanics. The probability of causing state i is calculated through the function below. Ei is the energy of state i, Ej is the energy of the state j.
But with SAPs, the number of states is 1 and the state is the most stable one.
The possibility to fold native conformation (PHPPH SAP) is of course 1.
Compared with both models, we can obviously think that thanks to the addition of SAPs, we can increase the probability to fold correctly; the stability of native state is definitely increased.
Let's think about more complicated case. The number of residue is 6 and the sequence is HPPHPH. The possible states are shown below. Also, we excluded enantiomers and rotamers.
As we did in the simplest model, we thought the most stable state is the native state; the native state has -2EH as its energy. In this case, the possibility to fold as native structure (PHPPHPHwild) is below.
With SAPs, the possible states are shown below.
The probability to fold as native structure is below.
As we have shown in the simplest case, by the addition of SAPs, the probability to fold correctly is definitely increased.
As we have shown, circularization using SAPs can stabilize protein native structure. However, we should be careful about SAPs' characteristic; SAPs can limit the structure by circularization, but of course, if the stabilized structure is different from native structure, the addition of SAPs means that it increase the stability of the denatured structure. This can be shown in the model. If we add SAPs to the ends of HPHPHHPPPHHH model, the most stable structure is changed.
As shown above, native state's free energy is -5EH, but stabilized structure's lowest energy is only -3EH. This means that if we want to stabilize a protein with circularization using SAPs, we have to be careful about the difference between its native structure and stabilized structure. If they have huge difference, we have to add linkers not to break its native structure by circularization using SAPs.
[1] Dill K.A. (1985). "Theory for the folding and stability of globular proteins". Biochemistry. 24(6): 1501?9. doi:10.1021/bi00327a032. PMID 3986190.
[2] Rob Philips. (2008) "Physical Biology Of the Cell". Garland Science
In our project, we tried to stabilize protein structure by circularization using SAPs. About the detailed concept of circularization, please read circularization page. To think about the power of stabilization by circularization using SAPs, we used HP (Hydrophobic-Polar) model. HP model is a kind of simplified protein folding model and in this model, protein chain is given as zig-zag stick on 2D lattice. Each residue has the characteristic H or P (Hydrophobic or Polar). To calculate the stability of protein structures, in this model, if an H residue is next to another H residue without covalent bond, it decreases free energy because of hydrophobic interaction. In our model, the decreased energy by each hydrophobic interaction is defined as -EH. We added another characteristic SAP into this model. Through thinking about this model, we can simply think about the effect of SAPs reflected as the effect to probability to fold as native state. We thought SAPs interaction is so strong, so in the case we add SAPs at N terminus and C terminus, both ends are set next to each other in the model. So, let's think about the simplest model.
The simplest model is the model with the number of residue is 4 and the sequence is HPPH. In this case, without SAPs, the number of states is 4, excluding enantiomers and rotamers. The possible states and the energy are listed below. KB is Boltzmann constant 1.38064852*10-23 (J/K), T is temperature (K).
|
|
Fig. 1 |
Only the first one is stable and its energy is -EH. Because it's most stable, we thought it's native state. The probability to fold as native state (PHPPH) is below.
 |
To calculate this, we used canonical ensemble from statistical mechanics. The probability of causing state i is calculated through the function below. Ei is the energy of state i, E
 |
But with SAPs, the number of states is 1 and the state is the most stable one.
|
|
Fig. 2 |
The possibility to fold native conformation (PHPPH SAP) is of course 1.
 |
Compared with both models, we can obviously think that thanks to the addition of SAPs, we can increase the probability to fold correctly; the stability of native state is definitely increased.
 |
Let's think about more complicated case. The number of residue is 6 and the sequence is HPPHPH. The possible states are shown below. Also, we excluded enantiomers and rotamers.
|
|
Fig. 3 |
As we did in the simplest model, we thought the most stable state is the native state; the native state has -2EH as its energy. In this case, the possibility to fold as native structure (PHPPHPHwild) is below.
 |
With SAPs, the possible states are shown below.
|
|
Fig. 4 |
The probability to fold as native structure is below.
 |
As we have shown in the simplest case, by the addition of SAPs, the probability to fold correctly is definitely increased.
 |
As we have shown, circularization using SAPs can stabilize protein native structure. However, we should be careful about SAPs' characteristic; SAPs can limit the structure by circularization, but of course, if the stabilized structure is different from native structure, the addition of SAPs means that it increase the stability of the denatured structure. This can be shown in the model. If we add SAPs to the ends of HPHPHHPPPHHH model, the most stable structure is changed.
|
|
Fig. 5 |
As shown above, native state's free energy is -5EH, but stabilized structure's lowest energy is only -3EH. This means that if we want to stabilize a protein with circularization using SAPs, we have to be careful about the difference between its native structure and stabilized structure. If they have huge difference, we have to add linkers not to break its native structure by circularization using SAPs.
[1] Dill K.A. (1985). "Theory for the folding and stability of globular proteins". Biochemistry. 24(6): 1501?9. doi:10.1021/bi00327a032. PMID 3986190.
[2] Rob Philips. (2008) "Physical Biology Of the Cell". Garland Science
