Question: Why Still A Hydrogen Bond Between A Mutated Ligand And The Protein?
gravatar for Lynn
9.5 years ago by
Lynn150 wrote:

Normally, when there is a mutation on the residue of a ligand, it causes the folding to change. This will then causes the protein to not being able to bind to the ligand. If we were to study the interaction between both the proteins by studying the hydrogen bonds that exist between them, how can we explain if there still exist a h-bond between both the protein and ligand when one of the residue is mutated?

Experimental results has proven that when that particular residue (Leu) is mutated into another residue (Phe) for that ligand I am studying, there was a reduction in that protein's activity. But why still a h-bond in between?

ppi protein • 2.2k views
ADD COMMENTlink modified 9.5 years ago by Reyhaneh480 • written 9.5 years ago by Lynn150
gravatar for Neilfws
9.5 years ago by
Sydney, Australia
Neilfws48k wrote:

Not all mutations cause dramatic changes in structure or large effects on interaction. That's why you do the experiment: to see the effect, not to confirm a preconceived idea.

Without knowing the details of your system, it's difficult to say very much more. However, in some ways, Leu and Phe are not that dissimilar; both are amino acids with quite large, hydrophobic side chains, even though the side chain in Phe is a benzyl ring, not a branched chain as in Leu.

The most likely H-bond donor/acceptor in both cases would be the amino or carboxyl groups, not the side chains. So it may be that both Phe and Leu provide a relatively non-specific hydrophobic interaction which allows the H-bond to form; just more easily in the case of Leu due to the difference in side chain shape.

ADD COMMENTlink modified 10 months ago by RamRS27k • written 9.5 years ago by Neilfws48k

Thank you so much for your time in providing a helpful explanation! That clears my doubt. =)

ADD REPLYlink written 9.5 years ago by Lynn150
gravatar for Reyhaneh
8.9 years ago by
United Kingdom
Reyhaneh480 wrote:

Why not trying FoldX? I have been using tool for this purpose. Since you are not able to test this experimentally you need to use a tool. FoldX allows you to mutate a specific amino acid of your protein structure (e.g. as a pdb file) and will give you the pdb file of the mutated protein. If you use YaSARA and the FoldX plugin for it then it will also show you the changes in hydrogen bonds after mutation. you can see how the side chain moves and the changes in HB. I have been using this tool and I am happy with the results.

ADD COMMENTlink written 8.9 years ago by Reyhaneh480
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