PCA trajectory analysis

[Aashish Bhatt]

Dear Bio3D user

Sir/Ma’am I have a query about PCA problem.

I have performed PCA calculation for namd dcd file for last 50ns. My wild-type protein shows that total PC contributed 87% whereas the mutant PC is 70% variance. As I gone through the literature I have found that higher the PC indicates higher structure fluctuation and this property should be present in mutant protein.

I have attached PNG file can you please giving me any suggestion about the analysis and also the discrepancy in my result.

I have used http://thegrantlab.org/bio3d/vignettes/Bio3D_md.pdf this tutorial for our study.

‌

Best Regards

Aashish Bhatt

INST-Mohali

[Xinqiu Yao]

Hi,

‌

First of all, the percentage looks too high for a MD. You might want to check whether your trajectories have been fitted properly.

‌

Second, I don’t think higher percentage indicates larger variance (I would appreciate if you can point out the literature). To compare fluctuations, you can superimpose reside wise RMSFs of WT and mutant.

[Aashish Bhatt]

Hi Xinqiu

Sorry for late reply.

Sir can you please describe what is the meaning of trajectories fitting here.

The articles attached below suggested that due to large confirmation the percentage was increased.

https://onlinelibrary.wiley.com/doi/full/10.1002/jcb.29052

https://www.ncbi.nlm.nih.gov/pubmed/?term=Exploring+the+cause+of+the+inhibitor+4AX+attaching+to+binding+site+disrupting+protein+tyrosine+phosphatase+4A1+trimerization+by+molecular+dynamic+simulation

I have attached the image of RMSF for comparison.

Thanking you

With regards

Aashish

[Xinqiu Yao]

By fitting I mean superimpose every frame of the trajectory onto the same reference structure (e.g., the first frame). Otherwise, what you describe is rigid-body translation-rotation of your system, which is not of interest. In bio3d, it can be done by fit.xyz(). Take a look of the Trajectory Analysis with Bio3D tutorial for more detail.

[Aashish Bhatt]

Thank you sir for replying

I have carefully read the tutorial and last 10ns trajectory i have used for PCA analysis.

I have superimposed every frame of the trajectory onto the same reference(First PDB structure).

Now for wild type we got PCA score 53.58% and for mutant 83.31% . Now what can I say about mutant type protein pca percentage and if I am proceeding correctly?

and second thing sir the x-axis and y-axis is in angstrom or nanometer?

[Xinqiu Yao]

The mutant still looks suspicious but it could be true that the mutation causes large conformation changes. I recommend use VMD or similar programs to visually check if the ‘fitting’ was done properly (i.e., you shouldn’t see overall translational/rotational movement after fitting).

[Aashish Bhatt]

Thank you sir

I am looking into the trajectory.

and sir is x-axis and y-axis is in angstrom or nanometer?

I have attaching the link.

https://www.sciencedirect.com/science/article/pii/S0301462218304174?via%3Dihub

Kindly suggest me.

Best Regards

Aashish

[Xinqiu Yao]

It is in angstrom.