Docking of Clarithromycin which is a macrolide, with 23s r-RNA

HADDOCK
1

I had an assignment to dock Clarithromycin with two 23s rRNA ( one wild and one mutant )… I used HADDOCK 2.4 for this propose, with all default values. After getting the results I got 3 cluster for mutant and one for wild type and some graphical representation.
My question are-

  1. Was my approach correct?
  2. Why I hadn’t get equal no of clusters for both.
  3. How do I interpret which is the best cluster? and there are 4 structure in each cluster, so I do I know which structure is best in a respective cluster?
  4. What is the correct way to interpret the graphical data’s?
  5. For wild type my Z score was 0, but in mutant I got there there cluster and three z scores 1.3, -0.2, -1.1? which should i take? cause my hypothesis was "there will be better binding with wild type than mutant ".
2

I had an assignment to dock Clarithromycin with two 23s rRNA ( one wild and one mutant )… I used HADDOCK 2.4 for this propose, with all default values. After getting the results I got 3 cluster for mutant and one for wild type and some graphical representation.

First question is what kind of data did you use to guide the docking?

  1. Why I hadn’t get equal no of clusters for both.

Depends on the docking results.

  1. How do I interpret which is the best cluster? and there are 4 structure in each cluster, so I do I know which structure is best in a respective cluster?

Based on the HADDOCK core and and the first model within one cluster is always the one with the best (lowest) HADDOCK score.

  1. What is the correct way to interpret the graphical data’s?
  2. For wild type my Z score was 0, but in mutant I got there there cluster and three z scores 1.3, -0.2, -1.1? which should i take? cause my hypothesis was "there will be better binding with wild type than mutant “.

The z-score is purely a statistical measure. By definition if there is only one cluster it is 0. If two clusters, it will be +1 and -1.
I.e. should not be used to select clusters. It only tells you how many standard deviations is a cluster from the average score of all clusters

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  1. For your 1st question I build 3d structure of rRNA using 3DRNA web server and i used pdb file of Clarithromycin. Then i perform entirely on default settings.
4

Thank you for your reply and time. I think I understand the ans of my 2,3,4 & 5 th question. but please tell me my approach was correct…

5

But how do you define the interface then?

Default settings do require the definition of active residues.

Or did you do ab-initio docking?

6

I selected 1st 200 nucleotide as active residue as that was the limit showed there…

7

I.e. no information… In that case better to use the ab-initio mode of HADDOCK with centre of mass restraints
You will also have to increase the sampling.

Needs guru access.

Check out haddock2.4 tutorials are bonvinlab.org/education

8

Thank you so much for your guidance. I will try Ab-initio then…

9

Thank you So much for this Guidance… I will try ab initio then…