Re: [AMBER] Unexpected reaction occurred in QM/MM umbrella sampling

From: Qing Lv <lvqingjiejie.163.com>
Date: Thu, 20 Feb 2020 18:59:38 +0800 (CST)

Dear Andy,


Thank you for the advice. In my system, the substrate alcohol oxygen coordinated with a Zinc (which is a part of the enzyme) and the reaction I want to simulate is: a hydride (H-) transferring from the alpha-C of alcohol (R-C*H2-OH...Zn) to NAD+
The reaction coordinate is: the difference of (distance of C* to H-) and (distance of H- to NAD:C)
The unexpected reaction I said is: the Cys:S- (originally coordinated to Zinc) forms a bond with C* . So the substrate will covalently bind to the enzyme and cause an irreversible inhibition, that is why I say it is unreasonable.


Could you provide any further suggestions? Thanks.


Qing





At 2020-02-20 10:41:06, "Goetz, Andreas" <agoetz.sdsc.edu> wrote:
>Dear Qing,
>
>If you observe what you describe as an unreasonable reaction, then most likely your biasing potential is not suitable. You may have to find a different reaction coordinate. Since your question is rather generic I am afraid it is not possible to give more specific advice.
>
>All the best,
>Andy
>
>
>Dr. Andreas W. Goetz
>Assistant Research Scientist
>San Diego Supercomputer Center
>Tel: +1-858-822-4771
>Email: agoetz.sdsc.edu
>Web: www.awgoetz.de
>
>> On Feb 19, 2020, at 5:56 PM, Qing Lv <lvqingjiejie.163.com> wrote:
>>
>> Dear Colleagues,
>>
>>
>> I am doing an umbrella sampling of an enzymatic reaction using QM/MM. However, as the reaction coordinate exceeds a certain value, an unexpected reaction, which is obviously unreasonable, often occurs during the umbrella sampling. So, how to deal with such problem? The only method I can think is to impose additional restraints to avoid this reaction, but the additional restraints will probably affect the umbrella sampling (although the additional restraints are not related to the reaction coordinate).
>>
>>
>> Thanks,
>> Qing
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Received on Thu Feb 20 2020 - 03:00:02 PST
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