One question that comes to mind is, can you imagine a set of laws of physics and constants of nature, that gives rise to complex chemistry which does NOT have any inherent biases?
Will it not always be the case that there is going to be some collection of structures that are more stable in some environment than others?
They write:
During folding the amino acid sequence of a protein appears to be searching conformation space for increasingly stable intermediates which lead it step wise toward the deepest energy minimum for that sequence, which corresponds to its final native conformation (Ptitsyn & Finkelstein, 1980; Finkelstein & Ptitsyn, 1987). The process is driven thermodynamically via a succession of free energy decreases (Dinner et al., 2000). The process of folding is often pictured as being analogous to a ball finding its way down the sides of a complex rather irregularly shaped bowl to the bottom of the bowl, its final preordained and natural resting place, where the bottom of the bowl represents the natural free energy minimum of the fold.
(…)
However a fold is able to maintain and regain its native conformation in the face of these microchallenges because its native conformation, being a natural free energy minimum, acts as a natural attractor ‘‘continually drawing’’ all the parts of the fold back into its proper native conformation (the natural free energy minimum of the fold). And just as a ball in a bowl always ends up at the bottom of the bowl, a fold is also able to get back ‘‘home’’ or to recover its proper conformation along an infinity of different paths. In short, the folds are robust natural existents, whose proper forms are under the governance and supervision of natural law.
I’m left wondering whether it is even possible in principle that it could be otherwise.
It seems to me that a set of natural laws that is capable of giving rise to a chemistry that has the potential to form complex interactions we could recognize as an organism, a living entity, has to involve physical forces of attraction and repulsion, and structures (something like atoms even if not the ones we know) that carry those properties.
If you have entities with attributes that attract and repel each other of many different kinds, you’re going to get the same phenomenon Denton et al describes above. There will always be some “native conformation” that is the natural free energy minimum state of that assemblage.
Another problem I see is that it’s almost like they are ignoring natural selection as a process of transgenerational change. It is not clear to me how they are imagining the “attractor” in fold space is able to instantiate it’s attractive force across generations as some protein folds evolve. It’s important to remember that they’re not saying protein folds didn’t evolve, rather that it wasn’t natural selection that determined why some fold instead of anther did.
But that simply doesn’t make sense. The only way to ensure that some fold evolves in future generations would be to have natural selection, where mutations in the evolving protein fold are discarded or retained on the basis of how they affect the ability of the protein to adopt the fold.
Later they write:
We speculate that the fact that the robustness of the folds [which enables them to maintain their forms and dependent functions in the face of both mutational challenges and conformational disturbances due to the turbulence of the cell’s interior] is ‘‘natural’’ may have deep evolutionary implications. The robustness of biological systems is generally conceived of as being analogous to that of advanced machines utilizing such devices as feedback control, parallel circuitry, error fail-safe devices, redundancy and so forth (Keller, 2000; Kitano, 2002; Csete & Doyle, 2002). But such robustness which we suggest might be termed ‘‘artifactual robustness’’ is inherently complex and can only be arrived at after millions of years of evolution and is necessarily a secondary and derived feature of any biological system or structure. The robustness of the folds is a natural intrinsicfeature of the folds themselves and not a secondarily evolved feature. Robustness of this sort is ‘‘for free’’ and does not require the intervention of natural selection.
Right, the robustness of some particular fold owes to the physical properties of the atoms that make up the molecule. Why is that protein fold stable under these conditions? Well because the electrons in this part of the molecule are held in place by their attraction to the protons in this other part of the molecule. That’s physics. Nobody says natural selection is messing around with the laws of physics when some protein evolves.
Rather selection is acting on what it has to work with: Amino acids, and their properties of physical attraction and repulsion. Hence why some stable protein fold evolves is that it’s stability is an adaptive property. Mutations that destabilize it too much(or make it too rigid) are discarded because they negatively affect the protein’s ability to implement it’s function(or have some other side effect that impacts organismal fitness).
I think there have also been some recent developments in our understanding of the evolution of folding proteins from intrinsically disordered states, that contradict Denton et al’s case here. That stably folding proteins really do appear to evolve gradually, under natural selection, from less stable ancestral states.