| Step 1. |
Identify all pairs of positions i,j in the sequence alignment where at least 20% of the residue pairs have change, volume, and hydrophobicity that lie in the same 3D property bin φpqr. |
| Step 2. |
Evaluate mutual information score for all pairs of positions i,j denoted as conserved for the corresponding bin φpqr. |
| Step 3. |
Perform bootstrap replicate analysis and select positions i,j that meet the P value cutoff of 5 × 10-3. |
| Step 4. |
Investigate the selected residue positions in the hybrids for clashes based on the following criteria: |
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| Step 5. |
Hybrids are given a score equal to the number of clashes identified in step 4. |