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DNA polymerase

jharry
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2/6/2010 6:49:52 PM
Posted: 6 years ago
taken from nature.com

biologists initially speculated that most replication errors were caused by what are called tautomeric shifts

Today, scientists suspect that most DNA replication errors are caused by mispairings of a different nature: either between different but nontautomeric chemical forms of bases

Speculation and suspicion, is that all?
In nomine Patris, et Filii, et Spiritus Sancti. Amen
jharry
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2/6/2010 6:57:17 PM
Posted: 6 years ago
At 2/6/2010 6:49:52 PM, jharry wrote:
taken from nature.com

biologists initially speculated that MOST replication errors were caused by what are called tautomeric shifts

Today, scientists suspect that MOST DNA replication errors are caused by mispairings of a different nature: either between different but nontautomeric chemical forms of bases

Speculation and suspicion, is that all?

This is kind of broad, I was looking for a more exact answer. One more question.
What is the predominant theory/belief in the scientific community on the subject of life beginning here or coming from somewhere else? I'm sure the combined knowledge here is far more vast then my twenty minutes with google.
In nomine Patris, et Filii, et Spiritus Sancti. Amen
I-am-a-panda
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2/6/2010 6:57:59 PM
Posted: 6 years ago
At 2/6/2010 6:57:17 PM, jharry wrote:
At 2/6/2010 6:49:52 PM, jharry wrote:
taken from nature.com

biologists initially speculated that MOST replication errors were caused by what are called tautomeric shifts

Today, scientists suspect that MOST DNA replication errors are caused by mispairings of a different nature: either between different but nontautomeric chemical forms of bases

Speculation and suspicion, is that all?

This is kind of broad, I was looking for a more exact answer. One more question.
What is the predominant theory/belief in the scientific community on the subject of life beginning here or coming from somewhere else? I'm sure the combined knowledge here is far more vast then my twenty minutes with google.

Lol @ Schizophrenia
Pizza. I have enormous respect for Pizza.
Puck
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2/6/2010 7:04:10 PM
Posted: 6 years ago
At 2/6/2010 6:57:17 PM, jharry wrote:

What is the predominant theory/belief in the scientific community on the subject of life beginning here or coming from somewhere else? I'm sure the combined knowledge here is far more vast then my twenty minutes with google.

1. Abiogenesis

2. Followed far behind by seeding.

It will never be a scientific theory (in the strict usage of the word) as it would require a time machine. RNA world hypothesis for abiogenesis has substantial support.
jharry
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2/6/2010 7:11:59 PM
Posted: 6 years ago
At 2/6/2010 7:01:35 PM, Puck wrote:

Or if you like shiny pictures.

http://learn.genetics.utah.edu...

As a matter of fact I love shiny pictures. That was the exact site I found when I googled how they make mistakes. But still I couldn't find exactly how they make a mistake. This is from the shiny picture site.

Mutations result when the DNA polymerase makes a mistake, which happens about once every 100,000,000 bases.

I understand they make mistakes, and I understand how many times they will probably make the mistake. But I still haven't found how they make the mistake. I guess what I'm asking is this.

How does a polymerase have the ability to make a mistake. I can make a mistake, a cat can misjudge a jump. But how can a DNA polymerase make a mistake. Water still flows downhill right? Can it make a mistake and run uphill?
In nomine Patris, et Filii, et Spiritus Sancti. Amen
jharry
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2/6/2010 7:18:05 PM
Posted: 6 years ago
At 2/6/2010 7:04:10 PM, Puck wrote:
At 2/6/2010 6:57:17 PM, jharry wrote:

RNA world hypothesis for abiogenesis has substantial support.

Forgive me for my ignorance, but I need a little help now and then.

So life didn't come in on a meteor? Most of the scientific community supports that idea right? If you choose to continue with my questions (and I would understand if you didn't) you may need to put it in laymen terms, thanks. No insult intended, your dealing with a G.E.D. winner.
In nomine Patris, et Filii, et Spiritus Sancti. Amen
Puck
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2/6/2010 7:21:13 PM
Posted: 6 years ago
At 2/6/2010 7:11:59 PM, jharry wrote:

How does a polymerase have the ability to make a mistake. I can make a mistake, a cat can misjudge a jump. But how can a DNA polymerase make a mistake. Water still flows downhill right? Can it make a mistake and run uphill?

Ah ok. There's 3 stages it can occur. First the DNA needs to be 'unzipped' to be read, and sometimes this will not occur perfectly, resulting in a flawed 'read' so that when it is copied (from a flawed read) it varies from the original. Then the base pairs need to be matched up again (zipped back up), the errant copy can produce errors due to its different form, lastly environmental factors such as a chemical or a virus can produce errors by interfacing with the process.
Puck
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2/6/2010 7:23:24 PM
Posted: 6 years ago
At 2/6/2010 7:18:05 PM, jharry wrote:
At 2/6/2010 7:04:10 PM, Puck wrote:
At 2/6/2010 6:57:17 PM, jharry wrote:


RNA world hypothesis for abiogenesis has substantial support.

Forgive me for my ignorance, but I need a little help now and then.

So life didn't come in on a meteor? Most of the scientific community supports that idea right? If you choose to continue with my questions (and I would understand if you didn't) you may need to put it in laymen terms, thanks. No insult intended, your dealing with a G.E.D. winner.

It's more, while there is that possibility, there is no evidence to assume so. RNA basis (organic chemistry) has the benefit of not needing external agents (outside Earth) for the process to occur, plus is growingly gaining lab support through replication.
jharry
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2/6/2010 7:33:32 PM
Posted: 6 years ago
Good, I understand the third stage. I understand how something from outside can interfere with the process. Maybe it's the words that are getting in my way. Thank you for using illustrations I can better understand. But I still have trouble getting my head around it because of the terms. Unzipped and read mess me up because these words are used to describe intelligent decisions and actions. A computer can unzip files and read data, but it only does these functions at the choosing of the writer of the program and the user. I've heard that a computer can't makes mistakes, it's the dummy at the keyboard that is the major malfunction. Is the final answer to this question "it just does"?
In nomine Patris, et Filii, et Spiritus Sancti. Amen
jharry
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2/6/2010 7:38:15 PM
Posted: 6 years ago
At 2/6/2010 7:23:24 PM, Puck wrote:
At 2/6/2010 7:18:05 PM, jharry wrote:
At 2/6/2010 7:04:10 PM, Puck wrote:
At 2/6/2010 6:57:17 PM, jharry wrote:
. RNA basis (organic chemistry) has the benefit of not needing external agents (outside Earth) for the process to occur, plus is growingly gaining lab support through replication.

You may have not understood where I was coming from. I wans't asking WHERE life began, as in RNA. RNA on earth is the answer. I was just wondering if RNA occurred
here or somewhere else? I'm pretty sure the answer is RNA occurred here and not on some other planet and then came here.
In nomine Patris, et Filii, et Spiritus Sancti. Amen
Puck
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2/6/2010 7:41:29 PM
Posted: 6 years ago
Polymerase is an enzyme. Enzymes roles are as catalysts for procedures that require increased activity. In terms of 'just does' it's a series of complex chemical reactions that occur within a body, cell(s) etc., that direct what, where and when activity occurs.
Puck
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2/6/2010 7:42:41 PM
Posted: 6 years ago
At 2/6/2010 7:38:15 PM, jharry wrote:
At 2/6/2010 7:23:24 PM, Puck wrote:
At 2/6/2010 7:18:05 PM, jharry wrote:
At 2/6/2010 7:04:10 PM, Puck wrote:
At 2/6/2010 6:57:17 PM, jharry wrote:
. RNA basis (organic chemistry) has the benefit of not needing external agents (outside Earth) for the process to occur, plus is growingly gaining lab support through replication.

You may have not understood where I was coming from. I wans't asking WHERE life began, as in RNA. RNA on earth is the answer. I was just wondering if RNA occurred
here or somewhere else? I'm pretty sure the answer is RNA occurred here and not on some other planet and then came here.

Yar, watch the vid, it will explain it in more detail. :)
jharry
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2/6/2010 7:43:01 PM
Posted: 6 years ago
At 2/6/2010 7:33:32 PM, jharry wrote:
Is the final answer to this question "it just does"?

I'm sorry. I can see how this might be offensive. Please continue, you may have an explanation I can understand.
In nomine Patris, et Filii, et Spiritus Sancti. Amen
Puck
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2/6/2010 7:50:10 PM
Posted: 6 years ago
Maybe I'm missing the point. :) The enzyme has a specific function in the body for which it performs. I guess 'it just does' may be accurate (in the sense of no grand designer) though I'm wary to assent to it in case it's misleading in some manner. Think of it as a series of complex 'if/then' commands within a series of chemical reactions.
jharry
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2/6/2010 8:11:46 PM
Posted: 6 years ago
At 2/6/2010 7:42:41 PM, Puck wrote:

Yar, watch the vid, it will explain it in more detail. :)

I watched the vid up to the point the next topic started, I watched the orgins of life, the rest I can understand. I understand the theory. I was just asking if this process occurred on earth or somewhere else and then came here. Thanks.

The answer is it started on earth right?
In nomine Patris, et Filii, et Spiritus Sancti. Amen
jharry
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2/6/2010 8:19:24 PM
Posted: 6 years ago
At 2/6/2010 7:50:10 PM, Puck wrote:
Think of it as a series of complex 'if/then' commands within a series of chemical reactions.

I tried that. I thought of a series of complex commands in a computer. If I "click" on the firefox icon on my desktop I will soon be directed to the firefox browser. I won't if the program (enzymes) don't do what they were programmed to do. But if the program is correct will I get a 100,0000,000 to one chance that clicking the firefox icon will take me to my computer? I believe I read that DNA is made up of enzymes and oxygen molecules right? Oxygen is in water right? Won't it change when applied to heat? Could I ever heat water on a fire and it not begin to steam?
In nomine Patris, et Filii, et Spiritus Sancti. Amen
belle
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2/6/2010 9:48:20 PM
Posted: 6 years ago
At 2/6/2010 8:19:24 PM, jharry wrote:
At 2/6/2010 7:50:10 PM, Puck wrote:
Think of it as a series of complex 'if/then' commands within a series of chemical reactions.

I tried that. I thought of a series of complex commands in a computer. If I "click" on the firefox icon on my desktop I will soon be directed to the firefox browser. I won't if the program (enzymes) don't do what they were programmed to do. But if the program is correct will I get a 100,0000,000 to one chance that clicking the firefox icon will take me to my computer? I believe I read that DNA is made up of enzymes and oxygen molecules right? Oxygen is in water right? Won't it change when applied to heat? Could I ever heat water on a fire and it not begin to steam?

alright, here goes. an enzyme is a protein with a certain shape, which means it can only bind certain molecules that fit- like a key and a lock. say the DNA polymerase "reads" a G. this changes the shape of the protein so that the active site (ie where it bonds with the nucleotide it is adding to the DNA chain) on the other is the ideal shape to fit a C (because, again, binding to the G changed the shape of the protein) however, T is relatively close in shape to C, and while its rare, the T molecule can fit in the active site of this enzyme that should only be able to bind Cs.

thats literally what happens. a molecule that is close enough in shape to fit the active site, even though it is in fact the wrong molecule, gets used anyways.

and DNA is most emphatically not made of enzymes. it is made of nucleotides- a sugar (deoxyribose) a nitrogen containing base, and phosphate groups.

enzymes are proteins, meaning they are made of amino acids. these are molecules consisting of an amine group (NH2) , a carboxyl group (COOH) and a "side chain" which varies between amino acids and gives each their unique properties.

DNA and proteins are both long chains of smaller molecules, but the molecules used in each case to build the chains are different.

and while water indeed contains oxygen, the chemical properties of an atom, especially its reactivity, are EXTREMELY different in the free state as opposed to when they are bonded to other atoms.

i hope some of that helps....
evidently i only come to ddo to avoid doing homework...
belle
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2/6/2010 9:50:55 PM
Posted: 6 years ago
At 2/6/2010 8:11:46 PM, jharry wrote:
At 2/6/2010 7:42:41 PM, Puck wrote:

Yar, watch the vid, it will explain it in more detail. :)

I watched the vid up to the point the next topic started, I watched the orgins of life, the rest I can understand. I understand the theory. I was just asking if this process occurred on earth or somewhere else and then came here. Thanks.

The answer is it started on earth right?

we can't know for sure, because no one was there to watch. however, most scientists agree that it probably started on earth rather than was brought by an asteroid, since even if it did come from space, abiogenesis would have had to occur *somewhere* and adding the extra step of the asteroid is unwarranted given our theories don't need it to account for the evidence we have.
evidently i only come to ddo to avoid doing homework...
jharry
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2/7/2010 12:19:11 AM
Posted: 6 years ago
belle,

Then it's not really like a key in a lock. A lock is designed to accept one key. A water molecule and a oil molecule are chemicals right? And they are designed to repel each other because of their chemistry right? Can they be forced to bind together? I don't know for sure but I think they can't, but if they could it would take some type of outside force to cause this to happen. But if left alone to do what they do then they would never combine. I know this because I've had head gaskets leak water into the crankcase of an engine. You pull the dipstick and out comes water first and then oil. Broken down into there smallest particles tey may appear to bind but if left alone long enough they will group together(another trait they are required to follow due to their chemistry) and become separate masses. A water drop in zero gravity will make a sphere, it is required to. I'm sure there is better terminology then "they are required to" but I hope you get my drift. If a T can fit in a G one time then it can fit every time? A T prefers a T but it can go in a G if it has to, unlike the water and oil? This may be a stupid question but "tells" DNA there is something wrong so that it can correct it? I may be having trouble giving molecules decision making capabilities in DNA and not in water molecules. Water doesn't make a mistake and run uphill and then figure it out and then turn around and make corrections, it can't. It's bound by what it is. What is the difference in an enzyme in my stomach breaking down food and an enzyme in my DNA? Is it special in some way? And if it is how did it get that way? Please excuse my ignorance on this topic, but if I don't ask I will never know. Thank you for the reply.
In nomine Patris, et Filii, et Spiritus Sancti. Amen
jharry
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2/7/2010 12:32:08 AM
Posted: 6 years ago
*Pull the drain plug not the dipstick*

And on your second post. I was looking for evidence just the common excepted belief/theory or what ever you call it most widely supported in the study of the origin of life in the scientific community. That answered my question, thank you all for the responses.

So was this an "accident" for lack of a better word? Everything was int he right order for this to happen at the right time? I'm not pushing creator or anything with this question, just a simple question.

And is evolution more purpose driven? Food and reproducing? Again, not pushing a Creator. It seems to me evolution is more purpose driven then the origin of life. The better equipped one is to eat and produce young the better odds that creature is to survive and pass on genes? Like water is getting low of food or monsters eating all my babies so if I'm better equipped due to genetic mutations or whatever and I can survive on land where food is abundant and less baby eaters then I will pass on genes and make more better equipped creatures to continue life. Deep breathe. In a nut shell?
In nomine Patris, et Filii, et Spiritus Sancti. Amen
Kleptin
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2/7/2010 6:51:34 AM
Posted: 6 years ago
@jharry

Hello. I'll give a basic rundown of all your main questions starting with the most theoretical.

The first thing is that things are not designed for any purpose. You stated that oil and water were designed to stay away, this is not true. Oil and water simply have properties in the molecular level that make it appear that they are staying away from each other macroscopically.

Microscopically, there is a layer where oil and water do mix. This is because molecules are constantly mixing, constantly moving, and constantly acting. In fact, the motions can be abused such that we can force oil and water to mix. The method is something called homogenization.

If you have ever seen fresh milk as opposed to the milk from the supermarkets, you will notice the difference. Milk is made from fat in water, and when it comes from the cow, it has a small tendency to separate. Homogenization forces them together.

So no, oil and water were not designed to stay away from each other. It's merely a manifestation of how we interpret things.

This is the same for DNA polymerase. Although we believe DNA polymerase has a single purpose, transcribing DNA, it actually is nothing more than an enzyme.

DNA polymerase can occasionally make mistakes simply based on how it works. It forms polymers based on the template strand according to what is around it.

As you know, A,T,C,G are the nucleotides used to pair up. Each one has its pair, A with T, C with G. I'll knock out the irrelevant details, but the main issue is that sometimes, the pairs are mismatched.

Wait, that's absurd, right? How can DNA polymerase make mistakes? It's a machine. Machines make mistakes too, just at a much lesser rate. Imagine a newspaper printer that is fed paper, and prints out newspaper. Don't tell me you've never seen a misprinted paper, one that was poorly aligned on the margins, or perhaps an upside down page, or a missing page. These occur because the machine thinks what is doing is correct, but the paper might have been fed to it misaligned.

Same with DNA polymerase. In order to make base pairs, it needs to have the right bases. The mechanism is done in such a way that the A,C,T,G that are flying all around, are continuously hitting enzymes during the DNA replication process. It's like a medic working in a warzone. The chances that A can be paired with C, G, or another A exists, but of course, the percentage is very, very low. The chance that T will be bonded is very high.

The point is, the possibility exists. It's just the fact that all four are present to be used by DNA polymerase makes the possibility null.

There are medical conditions and drugs with mechanisms having to do with replacing nucleic bases with other substances that look like nucleic bases.

The main point? Everything makes mistakes because nothing has an exact function. Things only have mechanisms that work in a specific way, most of the time. It should be no surprise that DNA polymerase makes errors.
: At 5/2/2010 2:43:54 PM, innomen wrote:
It isn't about finding a theory, philosophy or doctrine and thinking it's the answer, but a practical application of one's experiences that is the answer.

: At 10/28/2010 2:40:07 PM, jharry wrote: I have already been given the greatest Gift that anyone could ever hope for [Life], I would consider myself selfish if I expected anything more.
sherlockmethod
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2/7/2010 10:00:51 AM
Posted: 6 years ago
Abiogenesis does not have a robust theory that unites all the studies like the theory of evolution does for biology. Deep sea vents have been researched and are gaining ground in the origin of life study. Deep sea vents, primordial soup, and the meteor investigations are not mutually exclusive. This has been in the news lately. Here is an article (blown out of proportion a bit) but still a good read. http://www.sciencedaily.com...

Deep see vents have a long history in abiogensis so the headline is misleading. The soup just seems to be in a deeper bowl. As for accident or purpose driven, I find it no more accidental or purpose driven than a storm or erosion.

Evolution is no more purpose driven than abiogensis or a storm or gravity. Your example is a rough example of natural selection which is included within the theory of evolution, but mutations are not necessary for natural section to occur; NS can act on mutations, however.

In several posts you mention water and ask if water can make a mistake and run uphill, and the answer is no. The laws of gravity apply to water (as long as gravity is present) all the time, as do chemical laws. Water no more decides to run downhill than a snowflake decides to arrange itself. Laws describe phenomena and are not broken like one breaks a criminal law.

"I believe I read that DNA is made up of enzymes and oxygen molecules right? Oxygen is in water right? Won't it change when applied to heat? Could I ever heat water on a fire and it not begin to steam?"

Water will go into a gaseous form if heated over a fire, every time (that is, unless another factor is added). But this reaction is not due to enzymes so this analogy does not work well. The water and oil example you provided does not fit well either. Water is a polar molecule (positive and negative charge) oil is not. We can mix them by using an emulsifier. The most common example used in high school chemistry is soap. All of these relationships are governed by chemical laws. Molecules have no decision making capabilities.

Now, enzymes increase the rate of chemical reactions. The lock and key approach has been rejected. Enzymes do perform specific purposes but are also flexible so an induced fit model was introduced.

The enzymes in your stomach serve a different function than the DNA polymerase. Both are still bound by chemical laws and do not make decisions. The issue with the DNA polymerase is that several opposing forces are at work. The rarity of mistakes can be attributed to several factors, but the shape of the binding pockets seems to be a big factor in preventing mistakes. Errors can results several ways and I will list some, and you can decide whether or not to research further:
1.DNA strand slippage
2.Misinsertion followed by primer relocation
3.Melting-misalignment and
4.Misalignment of a nucleotide at the active site

http://www.nature.com...

This article is the best I have found so far, but the other information comes from a standard high school chemistry book. Analogies work well in the learning process but one must be careful with them as false equivocation can occur. Thank you for your questions as I enjoyed finding out more about this process.
Library cards: Stopping stupid one book at a time.
belle
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2/7/2010 10:01:02 AM
Posted: 6 years ago
At 2/7/2010 12:19:11 AM, jharry wrote:
belle,

Then it's not really like a key in a lock. A lock is designed to accept one key. A water molecule and a oil molecule are chemicals right? And they are designed to repel each other because of their chemistry right? Can they be forced to bind together? I don't know for sure but I think they can't, but if they could it would take some type of outside force to cause this to happen. But if left alone to do what they do then they would never combine. I know this because I've had head gaskets leak water into the crankcase of an engine. You pull the dipstick and out comes water first and then oil. Broken down into there smallest particles tey may appear to bind but if left alone long enough they will group together(another trait they are required to follow due to their chemistry) and become separate masses. A water drop in zero gravity will make a sphere, it is required to. I'm sure there is better terminology then "they are required to" but I hope you get my drift. If a T can fit in a G one time then it can fit every time? A T prefers a T but it can go in a G if it has to, unlike the water and oil? This may be a stupid question but "tells" DNA there is something wrong so that it can correct it? I may be having trouble giving molecules decision making capabilities in DNA and not in water molecules. Water doesn't make a mistake and run uphill and then figure it out and then turn around and make corrections, it can't. It's bound by what it is. What is the difference in an enzyme in my stomach breaking down food and an enzyme in my DNA? Is it special in some way? And if it is how did it get that way? Please excuse my ignorance on this topic, but if I don't ask I will never know. Thank you for the reply.

you're making the wrong analogy. oil and water are *extremely* different. their properties are such that they tend to bunch together to the exclusion of one another. C and T are different, but only very slightly. in fact, the only difference is a switch in the position between a nitrogen and an oxygen and 2 extra hydrogens. the shape is mainly the same, the charge is similar.

locks are designed to fit only specific keys but that doesn't mean that one key will only work for one lock in all cases. if you have a key similar enough to the original key in shape, even though it doesn't fit exactly, it will still unlock the door. its not that the T can fit sometimes and not at other times. It can fit *badly* all the time. and if it gets encountered by the DNA polymerase under the right circumstances (ie the right angles and velocities for contact) it will get used even though technically speaking its the wrong molecule.

and btw, your stomach enzymes are the same way. they sometimes bind the "wrong" molecules too. but no one cares, because its really of no consequence to anything.
evidently i only come to ddo to avoid doing homework...
sherlockmethod
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2/7/2010 10:16:26 AM
Posted: 6 years ago
Belle,
The lock an key approach has been replaced with the induced fit model. Which seems to be what you are saying in this last post. You are certainly on the right track, but the lock/key analogy may be misleading.
Library cards: Stopping stupid one book at a time.