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That is right, is there a limitation, say Heisenberg's uncertainty principle or something that limits our understanding of machinery of enzymes at atomic level? Can we know how do they actually work?

As far as I can tell, there is no explanation of actual design and working principles of any enzyme at atomic scale. Even the nobel prizes are given to discoveries not related to molecular details but rather pathways in which enzymes are not the primary concern, they are just represented as simple geometric shapes.

PS: I know that we have the exact molecular structures of some enzymes discovered using crystallography techniques, but even then, do we know which parts execute which function and how?

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MD simulations.

Molecular Dynamics algorithms like Gromacs and AMBER aim to simulate atomistic mechanisms of biological macromolecules.

This video shows a good example of a resulting video from such a simulation for the CmAAT1 Enzyme, CmAAT1-Hex-aCoA complex. Much more data such as energy values and electrostatic interactions is available from the simulation, but that's not as pretty as the video!

enter image description here

Implicative mechanisms.

There are also telltale signs of active regions of crystal structures. Software like Consurf can show conserved residues. This implies possible biochemically important features like key structural or enzymatic residues, areas of a protein. The image below is from the consurf gallery and is based on the crystal structure 3COQ. Pink is areas of conservation. It therefor appears that those residues are involved in binding DNA.

enter image description here

Consurf is only one of many tools for identifying key residues. After these residues are identified, mutant knockouts of the protein can be made to see exactly how the function of the protein is altered. From that, a fairly good mechanistic model can emerge.

Uncertainty

"Can we know..."

The word "know" is a philosophically ambiguous word and I've gathered that scientists generally tend to avoid it. This is particularly true when it comes to the simulation side of things. It is generally best to regard MD simulations as an approximation of what happens.

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  • $\begingroup$ Thank you! I am thrilled by all that new information. So currently is this the borderline about molecular dynamics studies? And here is a follow-up question if you wish to answer: why conserved regions are the regions that get the job done? $\endgroup$
    – user13196
    Jan 14, 2016 at 2:17
  • $\begingroup$ One more thing sir, why scientists try so hard to visualize molecular interactions which requires a lot of computational power and sophisticated algorithms? Are these MD simulations used somewhere other than fancy scientific presentations? I mean, this is just an approximation, as you stated. Even though these algorithms follow some physical and chemical properties, could they be used in pharmaceutical studies? I believe no, it must require an excellent precision to design or find a fitting key for enzymes. $\endgroup$
    – user13196
    Jan 14, 2016 at 2:54
  • $\begingroup$ And I think simulation is absolutely not the right way to discover underlying principles of molecular dynamics. Think of it sir, a bulk of atoms(composed of electrons and a nucleus to emphasize unconsciousness) organized in such a way that they, as a whole, can manipulate organic compunds. This absolutely requires an unbelievable manifacturing process at an unprecedented precision level. With obviously underlying excellent design details which should be our actual purpose of research. Not the redundant, fancy visuals of these enzymes. What are your thoughts sir? Thanks.. $\endgroup$
    – user13196
    Jan 14, 2016 at 3:09
  • $\begingroup$ @m1clee I've responded to your points in the chat. chat.stackexchange.com/transcript/message/26824047#26824047 $\endgroup$
    – James
    Jan 14, 2016 at 3:29
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    $\begingroup$ @m1clee The folk from the Shaw lab in NYC who built the Anton MD HPC came to our lab the other day to show us their recent MD simulations. They are probably the world leaders when it comes to MD. Check out their work if you want to learn more deshawresearch.com/publications.html. $\endgroup$
    – James
    Jan 29, 2016 at 7:40

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