Hi Sorbhi,

The Geman-McClure weight (alpha) controls robustness to outliers. As this value 
is raised, more restraints are treated as outliers and down-weighted. This will 
allow local conformational differences where there are dissimilarities between 
target and reference structures.

So if you really really want the restraints to be used (e.g. if you're trying 
to force something to be more helical) then you can use a lower alpha. Though 
if there may be some real differences between the restraints and the true 
structure - e.g. if you're using restraints based on a homologue - then you 
might want to use as slightly higher alpha so that regions displaying larger 
discrepancies from the restraint targets will not be influenced by the 
restraints. If you're using self-restraints then it's a balancing act - you 
want the structure to be stabilised, but you also want to allow it to deform 
enough to allow local structure to find the correct place in the map.

In Refmac values around 0.01-0.02 are typical. In Coot it varies - potential 
use cases during model building can be more varied than in refinement. The 
overall strength of the restraint weights also plays a big part, so it's a case 
of trial and error. Maybe Paul can advise about his preferred strategy? 
Fortunately in Coot it's easy to try different values, and the real time visual 
feedback of refinement performance should make it intuitive to see whether the 
alpha should be increased or decreased, especially when looking at more 
difficult regions.

Paul's got some videos of this in action, e.g.: 
https://www2.mrc-lmb.cam.ac.uk/personal/pemsley/coot/files/movies/refine-example-nov.ogv

Regards,
Rob


> On 12 Oct 2020, at 13:44, Sorbhi Rathore <[email protected]> wrote:
> 
> Dear all,
> 
> Could anyone please suggest the best way to decide which German- McClure 
> Alpha value to use during refinement (both at a higher resolution and lower 
> resolution areas for a cryo-EM map)?
> I am using coot 0.9.1 pre EL(ccpem).
> 
> Best wishes,
> Sorbhi
> 
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