[AMBER] Computational methods to explain the small regioselectivity

From: Mu Xia <muxiachuixue.163.com>
Date: Wed, 24 Oct 2012 16:21:55 +0800 (CST)

Hi all,

I'm confused with my project and hope someone could give me some suggestions.

The experimental results show that enzyme E could catalyze the methylation of compound A. There are two active groups to be catalyzed in A when binding in relative position and the regioselectivity is 3:1.

My job is to explain the regioselectivity by computational means. So I calculated the binding free energy of the two binding positions and also compared the reaction barrier by using QM/MM. The results disappointed me.

Leave alone the results I have gotten, my feeling is whether it is appropriate to utilize computational methods such as MD and QM/MM to explain such a small regioselectivity (i.e. 3:1). Because this may be within the error range. My worry is when I submit my manuscript, the reviewers would reject for the reason I have raised above.

So my question is, is it scientific to explain the 3:1 regioselectivity by using free energy calculation from MD and reaction barrier calculation from QM/MM? If the answer is no, what is the best option?

Many thanks!

Mu Xia,
Zhejiang University, China
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Received on Wed Oct 24 2012 - 01:30:03 PDT
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