I’ll post some articles to get you started. But it’s a little worrying that you didn’t try to find them yourself. If you are “on a quest to understand biology well enough” then you should already be able to explore the basics of evolutionary theory and the basics of protein structure and function. Some of that information is right here in this thread (earlier, in the discussions of IDPs). So, below are some key articles that should help you understand some protein evolution-related concepts, but it’s up to you to do the work to figure them out. And in my opinion, it is inappropriate and a waste of my time to exchange posts with you if you do not intend to learn more.
Robustness in biology/evolution:
Andreas Wagner is one of the world’s best and his book The Arrival of the Fittest would be enlightening and enjoyable to anyone truly interested in evolution from a systems point of view, and especially to anyone interested in various aspects of biological resiliency. An article-length review is The role of robustness in phenotypic adaptation and innovation. Specifically on protein structure, and in fact on the kind of protein structure that seems at first glance to be stringently controlled and less tolerant of change, see The Robustness and Evolvability of Transcription Factor Binding Sites
A great review of robustness and evolvability by someone I know pretty well, also a world expert:
https://www.cell.com/trends/genetics/fulltext/S0168-9525(10)00110-1
Here is very recent review, focused on the level of development (neural development, my favorite). I can provide the PDF on request.
https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(18)30154-1
Variation in proteins (“protein diversity”)
This one should require no sources, since IMO everyone should know that diversity in individual organisms implies diversity in genes and therefore (at least part of the time) in proteins. But it’s worth noting that despite the fact that protein variation has been studied since the early days of molecular biology (here is a historical review of some classic papers from the 1960s), we have only recently (last decade or so) been able to catalog variation in genomes and genes and proteins with high throughput. Specifically in humans, the Exome Aggregation Consortium is cataloging protein-coding variation in large cohorts. Their first edition was published a couple of years ago.
The short summary is that variation in protein structure is common within populations, and this should be obvious on reflection to anyone who knows the tiniest bit about what proteins and genes do. If protein structural variation were not tolerated, then you would not be reading this.
Protein flexibility
I refer you to the preceding discussion of IDPs, but also to our knowledge of chaperones, “moonlighting,” functional switches induced by post-translational modifications, to name a few big ones that came to mind. Proteins are flexible in how they respond to changes (mutations), which is a form of robustness, and they are also flexible in what they can do. This, of course, is a generalization; tolerance of change varies over orders of magnitude. The point is that if you propose that a change in a protein must necessarily cause problems or precipitate network-wide adjustment, then you don’t know what you’re talking about.
Redundancy
Redundancy at the protein level was actually a somewhat vexing problem for biologists (like me) studying knockout mice in the 90s and 00s. (It’s still a problem but less vexing.) We would make a knockout for the purpose of studying the roles of a protein in development or physiology. The protein was known to do interesting things, so it was a candidate for the long and arduous process of making a knockout. And then at the end of the line… there would be no phenotype. No effect. Why? Big question, but in many cases the answer was redundancy. Protein X did in fact control process Y, but another protein could stand in when necessary. Maybe the backup is a closely related protein, and maybe it’s not so closely related. In some cases we still don’t even know how the deficit is made up. But the take-home message was clear: in many cases, there is functional redundancy in the system, such that removing an entire component won’t necessarily bring the system down.
In plenty of other cases, we know in advance that there is redundancy, functionally and/or structurally, in a biological system. It’s just one more reason why no biologist would suspect that a change to a single protein would necessarily be a big deal.
It’s actually fact.
Let’s stop here, because I think it is doubtful that we will have a discussion. In multiple places in your post, you dismiss biological knowledge as nonsense, you suggest that biologists (me in particular) are using fancy words to hide ignorance, you implicitly suggest that evolutionary biologists are dolts who can’t see obvious weaknesses in the theory. You are mocking the science, while showing us that you have no understanding of what it is. You ended with “help me understand,” but I doubt you want to understand. So. Please don’t expect me to walk you through the basics of protein function, or evolutionary biology. That’s your responsibility.