Dear All
I am working with beta-lactamase enzymes responsible for antibiotic resistance. I have made all the variants in the lab that are available in nature and going to test their kinetic and phenotypic ability against beta-lactam antibiotics. However, I am interested to see the possible structural changes in silica in between the wt and mutants due to point mutations. I had made models using SWISS-model and did not get that much visible structural changes.
1. Would you please advise me - should I do molecular dynamics, MD or PCA (principal component analysis) to get some enough data to conclude about the changes are due to point mutation
or
Please advise me what should I do and which free software I could use.
2. Which free tools I could use to see whether point mutation has a positive role to change the secondary protein structure i.e., protein folding or changes in the global % secondary structures?
Many thanks
M Himel
I would first check for the change in energy due to point mutation and then go for MD, if there is a significant change in the energy.
http://compbio.clemson.edu/SAAFEC/
https://zhanglab.ccmb.med.umich.edu/STRUM/
http://biosig.unimelb.edu.au/dynamut/
All the best!
I would first check for the change in energy due to point mutation and then go for MD, if there is a significant change in the energy.
http://compbio.clemson.edu/SAAFEC/
https://zhanglab.ccmb.med.umich.edu/STRUM/
http://biosig.unimelb.edu.au/dynamut/
All the best!
Hello Mahbubul Himel
As Rajesh Pal suggested, I would recommend to further investigate the point mutation effect through molecular dynamics simulation.
Based on the trajectories obtained from MD simulation, a lot of analysis can be utilised to investigate and compare the structural properties between the wt and mutant. Some basic analyses include RMSD, RMSF, Rg, PCA, Hbond, etc.
In terms of free software for MD, I personally use GROMACS and XMgrace.
However both of these runs on linux.
Do bare in mind that a short simulation may not provide enough information.
Good luck.
Dear Rajesh and Farrah
Thanks a lot for your valuable suggestion. I am going to start my task and will ask for further advice if I face trouble.
You guys are busy researcher so I appreciate the time you spent for me.
Many thanks
Mahbubul Himel
Hi all,
You can equilibrate the system with MD simulations. After that you need to calculate the free energy difference between these states. Because alchemical mutations like changing one amino acid to another resulting with a change in free energy. You can figure it out with creating a thermodynamic cycle between wild type and the mutant one.
Cheers,
Ali
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