You have two enzymes Ayain (left) and Colease (right) and experimental evidence that the green and blue amino acids shown above form an active site in each case. You wish to use Al to study the likely structure of the active site in detail. This will give you information to help select possible drugs that fit the active site and will be tested in future experiments. You know the amino acid sequence of each protein and produce Alphafold predictions with the Predicted Aligned Error shown above. You only have enough funding and time to study one of the predictions in more detail. Which do you choose and why? Ayain 1640 and 2000

Question

You have two enzymes Ayain (left) and Colease (right) and experimental evidence that the green and blue amino acids shown above form an active site in each case. You wish to use Al to study the likely structure of the active site in detail. This will give you information to help select possible drugs that fit the active site and will be tested in future experiments. You know the amino acid sequence of each protein and produce Alphafold predictions with the Predicted Aligned Error shown above. You only have enough funding and time to study one of the predictions in more detail. Which do you choose and why? Ayain 1640 and 2000
Colease 1521 and 861

GPT-4o mini · Answer

To determine which enzyme (Ayain or Colease) to study in detail based on the Alphafold predictions, we should consider the provided Predicted Aligned Error (PAE) values along with the overall qualitative information about the amino acid sequences and the active sites.

The PAE indicates the confidence level in the predicted structural alignment. Lower values suggest higher confidence in the predicted structure, meaning the predicted positions of the amino acids are likely correct.

Here are the PAE values for both enzymes:

Ayain:
- PAE: 1640 and 2000
Colease:
- PAE: 1521 and 861

From these values:

Colease shows a PAE of 861, which is significantly lower than both values for Ayain (1640 and 2000). This suggests that the prediction for Colease has higher structural reliability, particularly notable because the lower the numbers, the more confident the model is about the positioning of the amino acids.
The other PAE values indicate that while the prediction for Ayain may also be informative, it carries a higher degree of uncertainty in its structural model, given the elevated PAE values.

Considering the goal is to study the active site of the enzymes in detail, which will ultimately assist in selecting potential drugs, the enzyme with the more reliable structure prediction will likely yield more accurate insights into the active site conformation and its fit for potential drug candidates.

Recommendation:

Choose to study Colease.

The lower PAE values suggest a more reliable predicted structure for Colease, which will provide more accurate information regarding its active site. This will be pivotal for identifying and designing potential drugs that can effectively interact with the enzyme.