Question: what is exactly "protein folding energy"?
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gravatar for 2001linana
12 days ago by
2001linana20
2001linana20 wrote:

I was reading a sentence, saying "a positive folding stability change indicates that the mutation will stabilize the structure of the protein and vice versa." So what is exactly "a positive folding stability change" ? Any comments are greatly appreciated.

sequencing sequence • 77 views
ADD COMMENTlink written 12 days ago by 2001linana20

This isn't strictly a bioinformatics question so should probably be closed, but:

The energy of a protein structure is a measure of its stability. A protein will (nearly) always want to adopt the lowest energy conformation it can in a given environment, subject to constraints on its actual structure imposed by the sequence and arrangement of the residues.

A mutation will stabilise a protein if it results in the protein having a lower overall free energy. This would usually be through the creation of new hydrogen bonds or something, or perhaps by altering the solubility of the protein etc. The opposite is therefore true - a mutation which causes a protein to be less hydrophilic for example, will make it less stable in solution, or might mean its structure is more 'fragile'.

Generally speaking, mutations which destabilise a structure will be selected against.

ADD REPLYlink written 12 days ago by Joe18k

So do you mean that a mutation will almost always stabilize the structure of a protein? By the way, why is this not a bioinformatics question ?

ADD REPLYlink modified 12 days ago • written 12 days ago by 2001linana20

Because you're asking about a general topic in biology/biochemistry, not specifically about bioinformatics uses/implementations of the concept of protein free energy. Its a grey area so I have left it open for now, but it was just to warn you not to be surprised if someone does close it.

So do you mean that a mutation will almost always stabilize the structure of a protein?

Quite the opposite. Most mutations are neutral (synonymous), so they have no effect on the protein because of the redundancy in the codon. Where a mutation is non-synonymous however, it is far more likely that it breaks the protein than improves it (there are many ways to ruin a protein, and only a select few ways to improve one). However, you are less likely to see these deleterious mutations, especially if the mutation itself is lethal, as the organism will likely not survive or be prevalent enough within a population to be observed.

ADD REPLYlink modified 11 days ago • written 11 days ago by Joe18k

One of my coworker once told me that, some mutants tend to die out and some mutants tend to prosper. Does this have something to do with the stability of the protein it's involved with then?

ADD REPLYlink written 12 days ago by 2001linana20

Well some mutants dying out, and some prospering is just the dictionary definition of evolution essentially - so yes, that's true.

It can have something to do with the stability of a protein, but that is one small part of a much larger picture. There are a wide range of reasons a mutation might lead to that variant dying out and they aren't always connected to protein function (of which stability is merely a subset as well), though often they may well be.

Your question is a bit too broad to answer very usefully, but think of the following as a fairly stark example:

If a protein is essential to the life functions of the given organism (let's say its DNA polymerase for example), then a mutation in that gene will mean that organism will very quickly die. That mutation might be something as drastic as a frame-shift, resulting in a truncation of the protein which would mean its essential biophysical properties change, and whole functional domains might be missing. Because this is lethal almost instantaneously, you are highly unlikely to ever find this mutation because the selection pressure is so strong. If the mutation is something comparatively trivial, such as a switch from a Glycine to an Alanine in a non-critical location, the protein might be ever so slightly less effective, but the organism may live on largely unimpeded. This variant could be driven to fixation, or it could be purified out, depending on the exact phenotypic consequences.

ADD REPLYlink modified 11 days ago • written 11 days ago by Joe18k
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