Genesis Insertion Site Predictor v3: Two Structural Mechanisms Govern Domain Insertion Permissibility

Key Points

• This study aims to enhance the Genesis Insertion Site Predictor's ability to identify permissible domain insertion sites in proteins.
• Expanded validation using 87 experimentally validated domain insertion sites from six structurally unrelated proteins.
• Utilized B-factor z-score and combined model for assessing insertion permissibility.
• Introduced a web API for user accessibility without the need for GPU or training data.
• B-factor z-score achieved a mean AUC of 0.782 across all six proteins (p=0.0016).
• Functional dispensability identified as a new mechanism influencing insertion permissibility.
• Combined model yielded an AUC of 0.881 for enzymes with defined active sites.