SAMPDI

SAMPDI predicts changes in binding free energy of protein–DNA interactions caused by single amino acid mutations to assess mutation impacts on DNA-binding affinity.

Key Features:

• Methodology: Employs a modified Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) approach augmented with knowledge-based terms derived from analyses of physicochemical properties in protein–DNA complexes.
• Benchmarking: Validated on experimentally determined binding free energy changes for 105 mutations across 13 proteins using data from the ProNIT database and recent literature.
• Performance Metrics: Shows a correlation coefficient of 0.72 when compared to experimental binding free energy changes.

Scientific Applications:

• Disease mechanism analysis: Quantifies how single amino acid substitutions in DNA-binding proteins alter binding affinities to inform molecular interpretations of disease-associated mutations.
• Therapeutic target identification: Prioritizes mutations that substantially affect protein–DNA binding for downstream experimental characterization and therapeutic investigation.
• Genomics and personalized medicine: Supports interpretation of variant effects in genomics and clinical studies by predicting mutation-induced changes in DNA-binding affinity.

Methodology:

Uses a modified MM/PBSA approach that integrates traditional MM/PBSA calculations with additional knowledge-based terms derived from analyses of physicochemical properties in protein–DNA complexes.