Re: [AMBER] Problem in designing MD simulation based on Experimental data

From: Chris Moth <>
Date: Fri, 16 Nov 2018 08:16:40 -0600

Here are a few quick thoughts, from perspective of relatively little
expertise, but only fascination with the question you are working on.

1) 150ns is likely a very short time-scale to observe something definitive.
2) The experimental observation could have a wide range of molecular
explanations, involving changes in longer scale enzyme motions, gating,
etc.  You might not (even likely will not) see this in "average
structures" or simple "loss of a hydrogen bond" type solutions.
3) Biomolecular MD force fields are parameterized for "normal"
temperatures.  When chemical engineers use MD to simulate high
temperature molecular motion, they must move to force fields that
incorporate more anharmonicity in the bonding terms (as but one example
- rigid water models break down as well!)
4) You might consider contiuum solvation vs. explicit water, to extend
5) "Inactivation" may too simplistic interpretation of the experimental
result.  Surely there is some curve of increasing inactivation....

A great thing about this Email list is that others will read my notes
above, and shortly give you the right answers :)

On 11/16/2018 9:53 AM, Bharat Manna wrote:
> Dear All,
> I am working with some enzyme activity experiments in different solvents
> and temperatures. The enzyme seems to get inactivated (structural breakdown
> based on expt. data) at a temperature of around 80 °C. So, I designed an MD
> simulation (same enzyme class PDB structure was taken) with proper solvents
> at 353K (80 °C) using AMBER 18. However, I didn't find any significant
> structural changes in the enzyme during the simulation (150ns). Is it right
> to increase the temperature (e.g. 400K to 500K)? If yes, will the
> simulation results be applicable to support the experimental findings
> (performed at a significantly lower temperature)?
> Please help.
> Thank you.
> B Manna
> _______________________________________________
> AMBER mailing list

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Received on Fri Nov 16 2018 - 06:30:02 PST
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