<p>I would like to know the acceptable error margin for the lowest free energy of a protein. In other words, say, both Group A and B have determined the lowest free energy of the same protein in their respective labs. What is an appropriate error margin so that I can compare these two results?</p>
<p>I just came across <a href="https://www.criver.com/eureka/free-energy-calculations-in-drug-discovery" rel="nofollow noreferrer">this article</a>.</p>
<p>Now let me quote the following from the article.</p>
<blockquote>
<p>Note that we generally require predictions to be within 1 kcal/mol to
be useful, since 1.4 kcal/mol equates to a 10-fold difference in
binding affinity.</p>
</blockquote>
<p>Can we use this 1 kcal/mol as the acceptable error margin?</p>
<p>Edited:</p>
<p>from *(lehninger principles of biochemistry) and <a href="https://www.quora.com/Is-Kd-the-dissociation-constant-for-a-given-protein-ligand-pair-directly-correlated-to-binding-affinity-kcal-mol-Rosetta-Energy-Units-etc" rel="nofollow noreferrer">Is Kd (the dissociation constant) for a given protein-ligand pair directly correlated to binding affinity (kcal/mol, Rosetta Energy Units, etc.)?</a></p>
<p><a href="https://i.sstatic.net/uCjDo.jpg" rel="nofollow noreferrer"><img src="https://i.sstatic.net/uCjDo.jpg" alt="enter image description here" /></a></p>

CC BY-SA 4.0
2023-11-25T09:39:21.773Z
"... both Group A and B have determined the lowest free energy of the same protein in their respective labs .... " do you mean theoretically or empirically ... in both cases I would like to know more about standard ways to achieve that nowadays
pippo1980
CC BY-SA 4.0
2023-11-25T10:01:03.193Z
talking about "The maximal and current accuracy of rigorous protein-ligand binding free energy calculations" https://www.nature.com/articles/s42004-023-01019-9 ---> ...As our experimental reproducibility survey indicated that experimental RMSE is on average ~1 kcal mol−1, it would be an extraordinary challenge to ever have an FEP method that achieves an error truly statistically indistinguishable from the experimental error o.... So again is the error margin sought a theoretical or empirical one ??
pippo1980
CC BY-SA 4.0
2023-11-25T13:04:02.927Z
what kind of chemical interaction gives rise to a change of 1.4 kcal/mol ??
pippo1980
CC BY-SA 4.0
2023-11-25T13:32:48.790Z
@pippo1980, I had empirical determination in mind.
Omar Shehab
CC BY-SA 4.0
2023-11-25T13:33:48.937Z
@pippo1980, I do not know what kind of chemical interaction gives such rise. Sorry.
Omar Shehab
CC BY-SA 4.0
2023-11-25T13:47:48.250Z
dont worry , just curious about your question , but not reaaly knowledgable about it , you could try https://mattermodeling.stackexchange.com/ too : Matter Modeling Stack Exchange is a question and answer site for Matter Modelers: computational chemists, material scientists, particle physicists, data scientists, and anyone else who uses computational methods to study molecules and materials
pippo1980
<proteins><protein-structure><proteomics><structural-biology><alphafold>
Energy error margin for protein structures
# Energy error margin for protein structures

(Asked by: username_0 on 2023-11-25)

I would like to know the acceptable error margin for the lowest free energy of a protein. In other words, say, both Group A and B have determined the lowest free energy of the same protein in their respective labs. What is an appropriate error margin so that I can compare these two results?

I just came across [this article](https://www.criver.com/eureka/free-energy-calculations-in-drug-discovery).

Now let me quote the following from the article.

> Note that we generally require predictions to be within 1 kcal/mol to
> be useful, since 1.4 kcal/mol equates to a 10-fold difference in
> binding affinity.

Can we use this 1 kcal/mol as the acceptable error margin?

Edited:

from \*(lehninger principles of biochemistry) and [Is Kd (the dissociation constant) for a given protein-ligand pair directly correlated to binding affinity (kcal/mol, Rosetta Energy Units, etc.)?](https://www.quora.com/Is-Kd-the-dissociation-constant-for-a-given-protein-ligand-pair-directly-correlated-to-binding-affinity-kcal-mol-Rosetta-Energy-Units-etc)

[![enter image description here](https://i.sstatic.net/uCjDo.jpg)](https://i.sstatic.net/uCjDo.jpg)

**Tags:** proteins, protein-structure, proteomics, structural-biology, alphafold
> **Comments:**
> **username_1**: "... both Group A and B have determined the lowest free energy of the same protein in their respective labs .... " do you mean theoretically or empirically ... in both cases I would like to know more about standard ways to achieve that nowadays  
> **username_1**: talking about "The maximal and current accuracy of rigorous protein-ligand binding free energy calculations" https://www.nature.com/articles/s42004-023-01019-9 ---> ...As our experimental reproducibility survey indicated that experimental RMSE is on average ~1 kcal mol−1, it would be an extraordinary challenge to ever have an FEP method that achieves an error truly statistically indistinguishable from the experimental error o.... So again is the error margin sought a theoretical or empirical one ??  
> **username_1**: what kind of chemical interaction gives rise to a change of 1.4 kcal/mol ??  
> **username_0**: @pippo1980, I had empirical determination in mind.  
> **username_0**: @pippo1980, I do not know what kind of chemical interaction gives such rise. Sorry.  
> **username_1**: dont worry , just curious about your question , but not reaaly knowledgable about it , you could try https://mattermodeling.stackexchange.com/ too : Matter Modeling Stack Exchange is a question and answer site for Matter Modelers: computational chemists, material scientists, particle physicists, data scientists, and anyone else who uses computational methods to study molecules and materials  

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## 0 answers

