best amino acid substitution

Emir Khatipov khatipovNO at
Wed Oct 3 13:22:12 EST 2001

I believe that the best substitute would be the aa with properties closest
to Cys. I would address this question in the following way. Cys is a medium
size non-polar aa. There is a so called Dayhoff matrix substitution diagram
that you can find somewhere on the web that shows that the closest
substitutes for C are V,I,M,L, and T. However, I would also consider
hydrophobicity as a parameter for selecting which aa is a better substitute.
In this respect, F,L,V,M and A seem to be pretty similar to C. Next, I would
consider the structure. Here, S, V, A, I, L, M in order of preference seem
to be pretty good candidates. So, I would go for S or V.

Why are you need to replace C? You know that C can form disulfide bridges or
coordinate metal ions. If you are going after disrupting any of these
interactions, I would suggest making C to A substitution, because Ala
substitutions are basically what most people do when they want to figure out
how important a certain aa in a certain position of a sequence. No
substitution can be ideal, or course.

Hope this helps.

University of Chicago

"Marc Busch" <mgbusch at> wrote in message
news:9pe6p5$s27$1 at
> I am not a biochemist and have had conflicting answer as to what is the
> conservative substitution for Cys. I thought it would be Ser (exchange S
> O), but someone else suggested Ala.

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