No almost all docking algorithm treats protein structure as rigid body no flexibility allowed unless it is done purposefully, Flexible docking please see http://www.nature.com/nchem/journal/v6/n7/abs/nchem.1954.html

If you mean DURING the docking calculation, then probably not, depends on the kind of docking you're performing (flexible or rigid, as stated in Nilanjan answer).

In vivo, the ligand usually influences the conformation and structure of a protein when interacting with it. You are able to evaluate this in silico by making use of available computational techniques, such as Molecular Dynamics simulations.

YES! And this change is dynamic, I mean, you do not have A conformation, the conformation of the complex is changed continuously. When we dock a ligand, the obtained complex is a picture of the complex in a given instant.

There are docking programs that use the protein rigid (do not allow changes in the protein structure), this type of docking is called rigid-flexible. And there are docking programs or protocols (using more than one program) where these changes are allowed, here the docking is called flexible-flexible.

Also, if you want to considered the structure protein changes you should use other methods like complex optimization via semi-empirical, ab-initio calculation or molecular dynamic.

In the work attached, we compare a simple rigid-flexible docking with an optimization process. The optimized complex is 30% "better" than the docked complex.

http://dx.doi.org/10.12785/jocr/010101

Yes There is conformation changes occur  in protein during binding to ligand. Some proteins known as Disordered proteins shows disorder to order transition upon binding to its partner OR ligand means before binding to ligand proteins remain in disordered form but it undergoes Ordered form upon binding to its ligand.

Hello

Try IMPACT and DESMOND softwares. They give the molecular dyamics, the conformational changes in both the ligand and protein as would occur in-vivo.

YES.

Sometimes the changes can be very considerable, read these:

Bywater RP, Sørensen A, Røgen P, Hjorth PG. J Theor Biol. 2002 Sep 21;218(2):139-47. Erratum in: J Theor Biol. 2003 Apr 21;221(4):669. Construction of the simplest model to explain complex receptor activation kinetics.

Bywater RP. (2013) Protein folding: a problem with multiple solutions. J Biomol Struct Dyn 31(4) 351-362.

There is a whole database r elated to this subject, check it out:

http://fizz.cmp.uea.ac.uk/dyndom/

QUITE GENERALLY, AND ALL SHOULD KNOW THIS: A PROTEIN (ANY PROTEIN) CYCLES BETWEEN 2 (OR MORE) STATES ALL THE TIME, ONE THAT IS CONDUCIVE TO BINDING LIGANDS AND THE OTHER IS NOT. WHEN THE LIGAND IS PRESENT IT STABILIZES THE FORM THAT BINDS LIGAND (AND VICE VERSA). THERE IS NO "INDUCED FIT", THE TWO STATES ARE ENERGETICALLY ACCESSIBLE ALL THE TIME, ONLY ONE OF THEM IS FAVOURED IN THE PRESENCE OF LIGAND (AND VICE VERSA ...).

Hello Robert P Bywater,

What do you mean by "THERE IS NO INDUCED FIT"?

I understand that the state without a ligand should remains (almost) the same through time. On the other hand, the state with ligand should be different for each complex, so, the ligand induces an structural modification in the protein.

Regards.

NO INDUCED FIT question: I mean exactly that. There is no induced fit. A ligand does not come along and preform a rugby tackle on the protein "forcing" it to change shape. That is a ridiculous idea, and the people who propose it have never been able to explain what the mechanism of that would be, even less have they been able to account for the energetics of such a process. Please read what I said: the protein is already cycling through different states under normal thermal conditions. Two of these (maybe more, but two is enough and is the most common) are energetically accessible. In the absence of ligand, probably the apo-form is most highly populated, but when a ligand does come along, it will make use of the opportunity of when the protein is in the "open" form and bind to it. What happens next depends on what type of protein (and ligand) are involved. The ligand does not cause any structural modification of the protein, the protein switches between two states and the ligand recognizes and binds to only one of these states.

Finally, please read the recommended literature and visit the Dyndom site, then you will understand this better.

The magnitude of change ranges from difficult to observe to drastic and depends on the protein and ligand combination. 

Conformational selection model and induced fit model are simplified representations of real binding events. No binding event corresponds 100% to conformational selection or induced fit.

A given protein is populating a set of conformational states in the absence of the ligand. The relative populations of those states depends on their Gibbs energy. When a ligand binds, some states are binding competent and others are not. Then, the protein stabilizes (shift the equilibrium and increases the relative population of) those binding competent staes.

In a simple description we have two coexisting conformational states: the protein in a conformation compatible with ligand binding (A) and the protein in a conformation incompatible with ligand binding (B). If the Gibbs energy gap (conformational energy) between those states is sufficiently small, there will be a mix of both states, with significant populations of both conformational states A and B. If the ligand is present, then, it will bind to the protein and will shift the conformational equilibrium towards the A state. In this situation we could say there is conformational selection. On the other hand, if the Gibbs energy gap (conformational energy) between those states is very large, the protein will populate just one state (B), because the population of state A is negligible. If the ligand is present, then, it will bind to the protein and will shift the conformational equilibrium towards state A. In this situation we could say there is induced fit, because state A was no (or hardly) populated. Thus, conformational selection and induced fit are two extreme cases of a binding event. Adscribing a given binding event to any of the two model depends on the size of the conformational energy gap between the to states, A (binding competent) and B. However, no matter how large is the energy gap, rigorously, the two conformational states coexist.

In many cases induced fit will occur even if the energy gap is small. E.g. when a given domain in a protein moves over the ligand, because that protein conformation is not allowed in the absence of the ligand.

That was very well explained (Adrian Velazquez-Campoy). Your notion of "binding competent" is excellent an d gives a clear picture of what actually happens.

I am still very negative about the "induced fit" idea because it suggests that the ligand is somehow a high-energy particle hitting the receptor and "knocking it into shape" (like an asteroid hitting the earth, maybe). I'm not sure how the Latin word "inducere" translates into Spanish but the English equivalents are: introduce, overlay, persuade, seduce etc. I like everything else that Dr Velazquez-Campoy says however.

If a ligand can not induce conformational changes in a protein then, why we found different structures of the same protein with different ligands in the Protein Data Bank (PDB)? And also, why the active site of all of them have different structure?

I have already explained that, please read my answer carefully (and the references), also go to the DynDom website and you will see all these structures, shown pairwise with the active/inactive structures superposed on each other. The two forms crystallize into different shapes because they ARE different. In solution, state A will switch to state B, forwards and backwards all the time. You have both structures at the same time. The state that the ligand prefers to bind to will become relatively more populated if you add ligand. The other state will probably predominate if you do not have ligand. But both state A and state B are energetically accessible from each other under thermal (earth's median temperature)  conditions all the time. You do not need to invoke "magical" forces that are supposed to be possessed by a ligand that comes along and forces this switching to take place. If you want a crystal of the APO form, do not put ligand in your crystallizing dish, it you want the active form, make sure you have ligand present. Voilà. That is all you need to think about.

@Robert,

Another meaning of "to induce" is "to cause" or "to be the cause of". I agree with you. It is not that the ligand binds the protein and the "collision" creates a distorted conformation. There should be an equilibrium between coexisting conformational states and the ligand alters the populations of those states according to the relative binding affinities (and also the binding stoichiometries). The ligand cannot make the protein adopt a conformation the protein is not intended to adopt by itself. The ligand select those states that are binding competent and they increase their statistical weight (molar fraction) in the distribution of states.

@Ihosvany,

Different ligands interact in a different way (structurally and functionally) with a given protein. That is, different ligands select and increase the population (molar fraction) of certain conformational states. As different ligands have different shapes and functional groups, there is no reason why they should interact in the same way. In fact, there are oligomeric proteins showing binding cooperativity for a given ligand and no cooperativity for another ligand, indicating that their binding and the conformational changes coupled to their binding are not the same.

The change is dynamic, continually changing conformation when docked ligand and the result is a picture of the complex at the time.

Exactly !!

I thought that you could find the answer yourself. Carry out the docking and use any of viewers (like SWISS PROT Viewer) to see the changes at diffrent docking energy levels.

Everybody thanks, especially Mr Bywater , Campoy .

I think it was one of the best topic in R.G.

In the fact the idea of this question is arises from the function of protein to make disease that docking with drug can inhibit or treat the disease.

Actually i try to find and understand the mechanism of proteins (biological pathway) in body (and how to docking process treat the disease).

if you know a literature please mention it.

best regards. Akbari