We are interested in the surface area of the binding interface only. This is the amount of area that is exposed in the unbound state, and buried in the bound state. In other words, how much does SASA change upon binding.
If the binding interface buries a lot of surface area (high SASA), a lot of water is released from the protein surface and this leads to tighter binding. If the binding interface has a small surface area (low SASA), a small amount of water is released upon binding and this contributes very little to binding strength.
The description of DDG says:
ΔGbound - ΔGbound
I think that should be:
ΔGbound - ΔGunbound
Unfortunately, the link to the 1993 article mentioned gets just the abstract for most of us. The abstract does mention a "new statistic Sc", but that's about it.
It's possible to get a shape complementarity of -1 when starting with an extended chain. Otherwise, what's the range of possible values?
I found this letter somewhat helpful: http://148.79.162.84/newsletters/newsletter39/02_sc.html
Under heading "Cross comparison of Sc values", there's a list of the parameters that affect the value of Sc. So it seems there's no true unit of measure, just the results of a calculation done a particular way.
Still, it would be helpful to know what values to expect in Foldit.
The true Shape Complementarity ranges from 0.0 to 1.0, where 0.0 is a poor fit and 1.0 is perfect hand-in-glove. In practice, I haven't seen anything above 0.80 for a protein-protein binding interface.
The Objective will report an "error" value of -1 when your binder is too far away and is not making contact with the target. Mathematically speaking, it's still possible calculate an SC value for two distant surfaces, but the result would be nonsensical and possibly misleading.
The SC value comes from the dot product of two vectors, so it is unitless.
Hovering over the new metrics once they are calculated gives you suggested targets.
For example, on puzzle 1880, the hover bubbles show these values:
- "target DDG is -40 or less"
- "target SASA: 1500 or greater"
- "target shape complementarity is 0.6 or greater"
Are these values set as part of the puzzle design? Or are they just fixed values? I see the puzzle 1877 devprev shadow had the same values.
The SASA value in particular seems like it may be a stretch on the coronavirus puzzles, but then I haven't hit the DDG target either. Shape complementarity is easy by comparison.
We may set these targets specifically for each puzzle. But the values you listed are a good rule of thumb for all binder design problems.
For what it's worth, it does seem that the SASA Objective is producing unrealistically low numbers on Puzzle 1877 and 1880. This is probably a bug, but we're still looking into it!
