Re: [AMBER] Critical Isoform selectivity in MD

From: David Case <>
Date: Thu, 27 Sep 2018 11:46:52 +0000

On Mon, Sep 24, 2018, M RCC wrote:

> my protein of interest has two isoforms, (Let us say, IsoformA and
> IsoformB). Both have more than 80% of sequence identity. In this case, few
> inhibitors are more selective towards IsoformA, and few are towards B.
> Crystal structure of these compounds with both Isoforms are identical.
> Even the authors reported that there is no difference in the between
> binding mode of inhibitors in the crystal structures.

Given this information, it seems likely that a pair of MD simulations starting
from these structures should give nearly identical results, which is what you
report finding. You would probably need to find some deeper explanation for
differences in affinity. If the experimental selectivity preference is small,
this may be quite a difficult task indeed.


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Received on Thu Sep 27 2018 - 05:00:02 PDT
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