perhaps the only real way to find out is to sequence 20-50 different clones of 
the final library and see if you get decent randomisation.

Mark J van Raaij
Lab 20B
Dpto de Estructura de Macromoleculas
Centro Nacional de Biotecnologia - CSIC
c/Darwin 3
E-28049 Madrid, Spain
tel. (+34) 91 585 4616
http://www.cnb.csic.es/~mjvanraaij





On 1 Oct 2013, at 11:00, Hazel F. wrote:

> Dear CCP4ers,
>  
> Thank-you very much for your many and fast answers! But I suspect you 
> misunderstood my question- I am having problems with site-directed saturation 
> mutagenesis- I try to incorporate a multitude of mutations in to a library. 
> So I get mutations, but not correct represention of all the bases I would 
> like to incorporate at the relevant position. So for example in the 
> sequencing I attatched I wished to see N (G, A, C and T) at the  first 
> position but the bases are not equally present.
>  
> Can someone give me advice on how to get better incorporation of all bases? 
> Or is this quality of sequencing (see attatchment) normal?
>  
> Thanks in advance!
>  
> All the best,
>  
> Hazel
>  
> M.Sc. Hazel Fuchs
> Ph.D. Student of Biochemistry
> Department of Cellular Chemistry
> Medical School Hanover
> Germany
> 
> Von: CCP4 bulletin board [mailto:[email protected]] Im Auftrag von Hazel 
> F.
> Gesendet: Montag, 30. September 2013 17:19
> An: [email protected]
> Betreff: [ccp4bb] Off-topic: Site-directed saturation mutagenesis trouble
> 
> Dear CCP4ers,
> 
> Sorry for the off-topic email. We are currently experiencing a bit of trouble 
> with our site-directed mutagenesis and hope that some of you have experience 
> with this.
> 
> Our sequencing chromatgograms suggest that the primers are not of good 
> quality as the bases are not represented euqally or that the PCR did not lead 
> to good incorporatoion of the bases - see attatched PDF. Is this sort of 
> chromatogram the best we can expect? So my questions are: Where do you order 
> primers? Do you do any special synthesis or are there important requirements? 
> What kind of mutagenesis protocol would you use? What quality of 
> randomisation can one expect?
> 
> We would be very grateful for any advice you can offer us.
> 
> Thanks in advance.
> 
> All the best,
> 
> Hazel
> 
> M.Sc. Hazel Fuchs
> Ph.D. Student of Biochemistry
> Department of Cellular Chemistry
> Medical School Hanover
> Germany
>  
> <LibrarySeq.pdf>

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