How To Calculate The Contribution Of Interacting Amino Acids In Binding

Question

[Hari]

Hi all, I would like to know how to calculate the contribution of residues towards binding especially the interacting residues in a known (pdb) protein complex.I did look at the servers suggested for this question http://biostar.stackexchange.com/questions/8354/important-residues-for-protein-protein-binding However i would like to know if there are other servers or methods that can do this.For.ex one parameter that would give the contribution of these interacting amino acids would be the interaction energy.Can i calculate this without having to do docking or simuation?

Thanks in advance for your suggestions.

[Jan Kosinski]

Is a tertiary structure of the complex available?

[Hari]

yes it is for known structures.

[Hari]

3d structure is available,i have edited the question accordingly

[Hari]

Both Robetta server and Anchor are quite useful for predicting hot-spots,one is accepted answer but +1 for both the answers,thanks a lot

Answer 1

[Jan Kosinski]

Perform so called computational alanine scanning and prediction of hot spot residues.

Although you must refer to the recent literature for the currently best methods and their performances, I can suggest you some to start:

• Rosetta alanine scanning (download Rosetta or try to use it on Robetta server)
• a server (one of several) to predict hot spot residues http://kfc.mitchell-lab.org/upload.php
• FoldX, e.g. mutate all interface residues to alanines one by one and calculate energy differences.

[Hari]

Thanks for the suggestions

Answer 2

[Dkoes]

PocketQuery is the successor of ANCHOR. It has pre-calculated delta G (from FastContact, like ANCHOR) and delta delta G (from Rosetta) values for all the PPIs in the PDB. You can also submit your own structure, although this takes longer to process than ANCHOR due to the Rosetta and sequence conservation calculations.

PocketQuery is designed to support the identification of small-molecule inhibitor starting points, so it performs an analysis on all possible clusters of co-located residues and allows you to output the result to various pharmacophore search engines. However, by setting the cluster size to 1 and setting the view to Residue Centric you can explore the PPI interface at a per residue level. Also, the viewer controls allow you to color interface residues based on their properties.

[Hari]

+1 for the suggestions