How To Create A Reliable Structural Homology Model Of A Missense Mutation?

Question

[Wayne]

So let me clarify: I am attempting to take a known crystal structure and change one amino acid, and then predict the structural changes that would ocurr. So homology model is not really the right description, more of a mutational model of a known structure. The services you described are great for high throughput queries but I need more information then they give. I'm looking to actually be able to make some functional predictions that would help one decide what the role of this or that mutant may be in cancer. Is a viable strategy to use Modeller with the native structure as a template to create a mutant structure? What tools would be useful for ab initio prediction of changes in the microenvironment surrounding the mutant... down to the level of saying things like " amino acid X is no longer able to hydrogen bond to amino acid Y" Or "This mutant decreases binding affinity at ligand binding site K" . Thanks a lot for your help .

Answer 1

[aravind ramesh]

Your question is not clear. If you already have a known structure why do you want to build a homology model ? If your Problem is to determine functional impact of nsSNP mutation, you can use several bioinformatics prediction tools like:

• HANSA(From Our Lab),
• Polyphen 2,
• Project HOPE,
• Mutation Taster,

• Condel and Many more.

  Read about all the methods, choose the program which suits your needs.

[Wayne]

So let me clarify: I am attempting to take a known crystal structure and change one amino acid, and then predict the structural changes that would ocurr. So homology model is not really the right description, more of a mutational model of a known structure. The services you described are great for high throughput queries but I need more information then they give. I'm looking to actually be able to make some functional predictions that would help one decide what the role of this or that mutant may be in cancer. Is a viable strategy to use Modeller with the native structure as a template to create a mutant structure? What tools would be useful for ab initio prediction of changes in the microenvironment surrounding the mutant... down to the level of saying things like " amino acid X is no longer able to hydrogen bond to amino acid Y" Or "This mutant decreases binding affinity at ligand binding site K" . Thanks a lot for your help .

[aravind ramesh]

Sorry for the delay in my reply. try "http://www.cmbi.ru.nl/hope/method" devloped by NBIC