SASA is the surface area of a biomolecule that is accessible to a solvent. If I define the amino acids forming binding cavity and measure the area of the surface, can that be considered as the total area available in that cavity or the area available for the inhibitor molecule...??
If yes, then can it be used to screen the inhibitors based on their total or topological polar surface area (TPSA)..??
Mostly agree with Luis above. Your approach sounds reasonable, but not optimal, and you'd probably be better off with a method specifically designed to estimate the size of a binding cavity - even placing the protein in your viewer of preference and measuring a rectangle that fills the cavity (just grab the atomic distances at the 3 principle axes) has a good chance of working compared to trying to get a SASA algorithm to estimate JUST the interior volume of the pocket, and accurately.
That being said: remember that shape plays a huge role in molecule/pocket binding as well. If your pocket is spherical, it'll accept much different molecules than if the same volume is a more long, extended, shallow pocket. It probably wouldn't be a terrible first-pass filter on a large library of molecules, but I wouldn't expect such a screen to output anything truly optimal. You'd want docking, or a much more robust QSAR, for that.
Thank you Dr. Luis F Pacios and Dr. William P Katt for your valuable guidance. Now I understood that SASA can provide the total area available in that cavity and it is more appropriate if the shape of the binding cavity is spherical.
My basic idea is to dock multiple ligands simultaneously (to validate synergistic effect) to a single binding pocket (in reference to competitive binding). So, if I know the volume of the binding pocket and total size of my 2 ligands, then is it not possible to say whether I can continue to dock them or reject that combination based only on the combined size of my ligands..?? Kindly suggest your valuable views..
It depends upon the nature of the docked ligands. If one is, say, highly hydrophilic on one edge, it could easily project partially into the pocket, and have the rest sitting along the protein surface, essentially capping the hole.
But, again, it's not a bad first-pass filter to try. Basically: if you have far too many potential solutions, and are worried about spending time on false positives, go ahead and use the filter. Kill early, kill cheap. But if you have relatively few cases, and are more worried about missing a correct answer, I'd just ignore the SASA calculation and do every paired docking.
I don't think so. Binding depends on shape and electrostatic complementarity between ligand and binding cavity. You can get two ligands that have completely different shapes but similar SASA or vice versa.
Hi Aditya,
CASTp showed SASA together with volume of pockets, would be helpful for you: http://sts.bioe.uic.edu/castp
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