Visualizing Amino Acid Substitutions in a Physicochemical Vector Space
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Abstract
A three-dimensional representation of the twenty proteinogenic amino acids in a physicochemical space is presented. Vectors corresponding to amino acid substitutions are classified based on whether they are accessible via a single-nucleotide mutation. It is shown that the standard genetic code establishes a “choice architecture” that permits nearly independent tuning of the properties related with size and those related with hydrophobicity. This work sheds light on the non-arbitrary benefits of evolvability that may have shaped the development standard genetic code to increase the probability that adaptive point mutations will be generated. Illustrations of the usefulness of visualizing amino acid substitutions in a 3D physicochemical space are shown using recent datasets collected regarding the SARS-CoV-2 receptor binding domain. First, the substitutions most responsible for antibody escape are almost always inaccessible via single nucleotide mutation, and change multiple properties concurrently. Second, it is shown that assays of ACE2 binding by sarbecovirus variants, including the viruses responsible for SARS and COVID-19, are more easily understood when plotted with this method. The results of this research can extend our understanding of certain hereditary disorders caused by point mutations, as well as guide the development of rational protein and vaccine design.
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SciScore for 10.1101/2021.07.15.452549: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on pages 14, 15, …
SciScore for 10.1101/2021.07.15.452549: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on pages 14, 15, 16, 17 and 18. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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