I would like to assess few enzyme proteins among the organism to understand the difference in their actions. The structure was modelled using homology modeling and same enzyme having different rate/kinetics in different organisms. Is there any possiblity to assses its functions through simulations or any theoretical calculations?
I agree with Pritam Kumar Panda you can follow
http://www.mdtutorials.com/gmx/lysozyme/index.html
Yeh, to me , you can compare the dynamics of hyrogen bonds in the catalytic site, or you can compare the position of amino acids close to substrate in both cases, it is intersting topic and gives evolutionary view point in action...
Yahya Sefidbakht You happend to see any related articles on this aspects? If there are no crystal structure availbe for the protein and catalytic sites are not yet studied/reported. How would you suggest to proceed?
Hello, yes there are many papers on homology modeling of enzymes and proteins, for example you can take a look at my publication list (the study on amylase) there, I have used a pdb structure for running md of unknown structure, then the amino acids involved in catalytic site tried to be described.
l thought weak bonds, reversible, other conditions pH, temperature control, conc.
All enzymes are proteins, so can follow same protocols.
Deas Nikhil Maroli ,
Molecular Dynamics simulations have limitations and you have to ask the model specific questions.
You cannot openly model the kinetics of an enzyme catalysed reaction and let the simulation to tell you the kinetic parameters like a black box. You need a very well calibrated system, and then ask one little detail at a time.
Even then each question requires significant sampling, meaning it is time-consuming and computer-demanding.
1. You first need evaluate how reliable is your homology model.
2. Then you need to make certain of the consistency in the packing of active-site chains.
3. Then you need to BUILD and VALIDATE the topology for each substrate and product you want to introduce to your simulations.
4. Finally, you need to formulate specific detailed questions, such as:
¿Are there differences between the dissociation constants of the substrate(s) or product(s) at the active site of the isoenzymes to consider (the template and your model, to start with)?
¿Are there any changes in the active-site amino acid groups directly taking part in catalysis?
¿Is the transition state the same?
¿Are energy barriers the same?
5. Each answer requires a different set-up a quite a lot of work.
6. Most answers are comparative, meaning you need to run the calculation with a well known reference and your target model.
7. Using QM/MM hybrid methods, and once you know with a good degree of certainty how the reaction is catalysed, then you can model the passage trough the transition state and make a comparative estimate of the energy barrier with your reference and target enzymes.
Best wishes,
Rogelio
There are numerous high resolution crystal structures showing the active sites of enzymes, especially those blocked by Fluoride in combination with Magnesium, Aluminium and Beryllium. In others Fluoride coordinates to the metal ion at the centre of Hemes. Which enzymes are you currently interested in Dr Maroli?
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