I doubt anybody can tell how your compound will bind without the full structure.

If there are similar compounds, it may be possible to postulate based on SAR. Otherwise, I think you can only find out via computer modelling or x-ray.

Hi Eugene,

Thanks for your answer. The binding affinity changes with the chirality. Which means the binding of chiral center is accounts for the binding affinity. I don't see why the entire structure is important because it's the same structure for R and S. Just the chiral center position is changed. Because FBS protein is made of several amino acids so I'm not sure which functional group of which amino acid is binding more efficiently with S isomers than R.

Are we talking about the same protein?

https://en.wikipedia.org/wiki/Fetal_bovine_serum

FBS major component is BSA which has 607 amino acids about 69kDa. Not very big I suppose in terms of proteins, but I am sure it still has multiple binding pockets. These pockets are 3D and only by knowing the whole structure is it even possible to contemplate how a molecule will fit into a pocket.

Hi Eugene,

I think I misunderstood. I thought you were talking about the complete structure of my organic compound. I was thinking perhaps I can go ahead and do FTIR analysis. That must highlight most common functional groups present in FBS based on the peaks and then I can compare the binding of those functional groups with the chiral center of my molecule to see which binding is the strongest. However, what I won't be able to know is how the orientation of R/S affects the binding affinity. That, I believe, can only be known from the computational structure of that particular functional groups in FBS and how it might interact with the chiral center of my compound. How do you think about that?

From the PDB, there are x-ray structure of BSA with ligands so if your compound is very similar to what has been done before, it is possible to postulate but even then there is no guarantee. Computation docking is probably your best way short of obtaining a x-ray of your compound with the protein.

Thanks again, Eugene,

I was thinking why not do the FTIR of 3 different compounds (a) FBS (b) R/S monomers (c) FBS+R/S monomers. I can then compare the functional group peaks and see if any of them are missing or added between (a) and (b). It is likely that say functional group A reacts with B to form C and THAT C is represented by a whole new peak visible in FTIR which might indicate the formation of a new bond between S-monomer and FBS but not present in R-monomer and FBS. It sounds like an easier way to get a indication of what might be going on over here. What do you think about that?

I am not a specialist in this, but I don''t think IR is sensitive enough to pick up such type of binding.

Hi Udesh,

Theoretically you can use FTIR but I am afraid you do not have a high resolution FTIR equipment. The most common FTIRs have 2-4 cm-1 resolution which is not enough high to study the molecular interactions.

The another problem might be the type of the FTIR equipment: ATR/reflective/transmission?

So, if you do have a high resolution ATR with a suitable crystal (the ATR crystals can have different usability in different regions) then you might have chances to find appropriate IR bands which characterize the associations.

Of course, you can use KBr/nujol matrices too in cases of other than ATR equipments, but then the sample preparation (e.g. amount of sample, sample/KBr ratio, etc.) have effects on the signals of small changes.

In a lucky case Raman spectroscopy may be also usable but sometimes the Raman-fluorescence may causes serious problems.

Hi Zoran!

You're right that the binding affinity is a function of the molecular symmetry. While I realized the difficulty in narrowing-down the interaction to a single functional group level, I came up with the proposal to rather study the interaction of my chiral molecule with individual amino acid. As the proteins are made up amino acids comprising of -COOH and -NH2 groups, it is likely that even within a huge protein, the interaction is happening at either or both of these locations (with -COOH and/or-NH2). As the amino acid structure is rather easy to "draw" and understand, I'm thinking to use MOLDEN to figure out the molecular symmetries.

I will consider if NMR can be useful in this scenario. Thanks again for your suggestion!

Hi Laszlo!

I'm not the resolution of the FTIR we have in our department. But, thanks for pointing out the resolution which I must consider. I believe we have a Transmission equipment. Thanks again for the suggestion!

A missing in these discussions is that chirality is always a 3D phenomena.

A  left hand and a right hand are symmetrical  mirror images of each other and a left handed glove and a right handed glove are symmetrical mirror images of each other.   Does not at all mean the left handed glove fits the right hand or that the right handed glove fits the left hand.  Each glove and hand have exactly the same number of fingers and in 3-D it matters.  Of course one can say the same thing of left-handed socks with right "handed "feet and with right "handed" socks versus left "handed" feet, and in this case,  not some much difference might be found.  If one then changes the model to shoes instead of socks,  again postulations about whether they fit the "opposite" mirror image foot will not necessarily be the same.

My total guess free from any compelling evidence is that an asymmetrical molecule exists that can fit an asymmetrical binding site better than any symmetrical molecule can.  And of course a very large number of asymmetrical molecules will not fit an asymmetrical site better than some symmetrical ones will .    .        .

alpha- and beta-Endosulfan are structural analogs in which beta-isomer is symmetrical and alpha-isomer is asymmetrical.  The laws of symmetry are not at all violated because the asymmetrical isomer is an equimolar mixture of two compounds, both of which are asymmetrical.

Hi Dr. Schmidt,

Thank you for your comment and to try and explain why this might be happening based on chirality. But, I think you missed my point. I am trying to figure out the "how" part rather than the "why" part.