I need to explore the impact of couple of mutations in a huge membrane structure which itself is a de novo model of ~2200 residues. I would like to find out the impact of these mutations by generating the single and double mutant models through molecular dynamics. Can anybody please suggest some specific consideration what aspects to be explored for eq. conformation variations, binding affinity with relevant to wild type model. Please suggest some detailed criteria to be followed for the detailed exploration of the mutations through in silico means.
Thank U
Hi Nanadakumar,
There is a very informative discussion going on ResearchGate. Please follow the link.
https://www.researchgate.net/post/Can_anyone_help_with_point_mutation_by_VMD
This will help you by answering your questions and also if you face some problem in future you know where to look.
Cheers!!!
Hi Nanadakumar,
There is a very informative discussion going on ResearchGate. Please follow the link.
https://www.researchgate.net/post/Can_anyone_help_with_point_mutation_by_VMD
This will help you by answering your questions and also if you face some problem in future you know where to look.
Cheers!!!
Dr. Nandkumar, you will have to consider following points.
First carry out model validation, because model has been constructed by de novo method. Also find out which portion will be in the membrane. This can be achived by submitting your model to server which calculates hydropathy index.
Second... once you have idea about , how your protein will position itself into the membrane, then you can carry out the in-silico mutation. You can use Chimera for the mutation purpose, which has option for rotamer change,
Third .. Build the system , which has protein immersed in membrane and asscoiated water molecules. For this purpose VMD can be used.
Fourth.. carry out MD simulation on wild and mutatnt protein.. Extensive.... approx- 50-60 ns.
Fifth... compare the results. You can do free energy analysis, essential dynamics etc...
@ Mr. Vikash: Than you for the clean explanation. I had gone through the same steps in my earlier studies also. I am more interested to explore them conformation wise in addition to energy analysis. Any way your suggestions helped me what to go through further.
Thank you....
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