Can You Differentiate A-T and T-A Base Pairs in DNA Grooves?

[gracy]

I know major groove occurs where the backbones are far apart and minor groove occurs where they are close together.
But I don't understand it. I don't see any difference in both of these grooves

 

[Ygggdrasil]

It's helpful to look at a base pair from the top view, looking down the axis of the helix:

(https://www.ncbi.nlm.nih.gov/books/NBK26806/)
The major groove and minor groove present different combinations of hydrogen-bond donors, hydrogen-bond acceptors, and other groups. In particular the minor grooves look very similar across the different types of base pairs whereas the major grooves look very different. Therefore, proteins that bind DNA regardless of the sequence often interact with the minor groove whereas proteins that interact with only specific sequences of DNA interact with the major groove.

 

[gracy]

In particular the minor grooves look very similar across the different types of base pairs whereas the major grooves look very different.

I did not understand.

 

[jim mcnamara]

A really bad analogy:
think of the minor groove as a 'generic' address in New York City: Apple St., New York, New York
Major groove is a special address: 1010 E Apple St., New York, New York.

If you ask a cab driver to take you to a generic (minor groove) address he has lots of places to 'fit' the request. If you give him a non-generic address (major groove) his 'fit' is decidedly limited. One place only.

Now:
Imagine 'yourself' as a molecule looking to bind to sites on a DNA molecule. If you can only bond with very specific places which site is 'best fit'? Major groove. If almost any old place would be okay to bond with, then where? Minor groove.

 

[Ygggdrasil]

Proteins can interact with DNA by both interrogating the shape of the base pair (for example, a T has a methyl group at one end, shown in yellow, whereas the C lacks a methyl group at that position and would not have that feature sticking out there) and through hydrogen bonding (where it can either interact with a hydrogen bond donor, shown in blue, or a hydrogen bond acceptor, shown in red). The diagram I posted shows the arrangement of these groups in both the minor and major groves of the DNA. Looking only at the order of these groups in the minor groove can you tell an A-T basepair from a T-A basepair? What if you look at the major grove, can you tell apart an A-T basepair from a T-A base pair?