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from IPython.display import Image
%pylab inline









    



Populating the interactive namespace from numpy and matplotlib

AncGK Family

Structure of the family

PDB files being used currently

We are looking at 3 pdb files with configurations of the GK family.

1EX6 ~ describes the structure of the open state
1EX7 ~ describes the structure of the closed state
4F4J ~ describes the structure of a S35P mutation. Exhibits reduced motion between the closed-opened state.

Dynamics of the system

We are going to sample the free energy landscapes of these different configurations using metadynamics. The "interesting" behavior in these enzymes/domains are the motion of the GBD and LID. Thus, we will be watching the distance between these two lobes and the dynamics at the hinge region between these two lobes.

The purpose of the sections below are to define these regions and collective variables necessary for the simulations.

The Open State



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Image(filename="figures/1ex6.png")









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Closed state



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Image(filename="figures/1ex7.png")









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Image(filename="figures/layer.png")









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The image above aligns the open and closed state, demostrating the change in position of the GBD. This defines our first collective variable and reaction coordinate for our simulation. Notice there is a significant change in the position of this lobe.



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Image(filename="figures/distance.png")









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We define the two lobes of the protein, and monitor the distance between their center of masses. The image below shows how defined the GBD and LID regions of the protein (the lobes of interest).



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Image(filename="figures/region_layer.png")









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GK with S35P mutation

A mutation, S35P, in the "hinge" region of the proteins above drastically changes the functionality of the protein. Thus, we will also sample the free energy landscape of this mutated protein and monitor the dynamics of the system around this mutation as well. The image below shows the struction of this protein.



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Image(filename="figures/4f4j.png")









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Proline vs. Serine Mutation

The distinctive cyclic structure of proline's side chain gives proline an exceptional conformational rigidity compared to other amino acids. This "rigidness" seems to inhibit the folding behavior of GK enzyme, and lead to new functionality (opposed to the Serine).

We will be observing the torsion angles around this amino acid, and analyzing possible conformations from Ramachandran Plots ($\phi$ vs. $\psi$).

Proline hinge region



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Image(filename="figures/hinge.png")









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Image(filename="figures/hinge_a.png")









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Serine Hinge Region



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Image(filename="figures/hingeS.png" )









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Image(filename="figures/hingeS_a.png" )









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