Body: <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>
  
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2023-11-25T09:39:21.773Z
Comments.Text: "... 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
Comments.UserDisplayName: pippo1980
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2023-11-25T10:01:03.193Z
Comments.Text: 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 ??
Comments.UserDisplayName: pippo1980
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2023-11-25T13:04:02.927Z
Comments.Text: what kind of chemical interaction gives rise to a change of 1.4 kcal/mol ??
Comments.UserDisplayName: pippo1980
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2023-11-25T13:32:48.790Z
Comments.Text: @pippo1980, I had empirical determination in mind.
Comments.UserDisplayName: Omar Shehab
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2023-11-25T13:33:48.937Z
Comments.Text: @pippo1980, I do not know what kind of chemical interaction gives such rise. Sorry.
Comments.UserDisplayName: Omar Shehab
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2023-11-25T13:47:48.250Z
Comments.Text: 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
Comments.UserDisplayName: pippo1980
Tags: <proteins><protein-structure><proteomics><structural-biology><alphafold>
Title: Energy error margin for protein structures
ThreadText: # 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**: @username_1, I had empirical determination in mind.  
  > **username_0**: @username_1, 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
  
  