PIIMS

PIIMS identifies mutation hotspots at protein–protein interfaces and quantifies the effects of amino acid substitutions on binding free energy using computational alanine scanning, molecular dynamics, and one-step free energy perturbation.

Key Features:

• Mutation Hotspot Identification: Performs computational alanine scanning to pinpoint hotspot residues that contribute disproportionately to binding energy within protein–protein interfaces.
• Comprehensive Mutation Scanning Analysis: Evaluates the effects of diverse amino acid substitutions at interface residues to estimate changes in binding free energy.
• Integration with Molecular Dynamics and Free Energy Perturbation: Computes binding free energy changes using molecular dynamics simulations combined with one-step free energy perturbation.
• Validation and Performance: Validated on a dataset of 1,341 mutations across 50 protein–protein interactions, reporting a correlation coefficient R = 0.75 between predicted and reference binding free energy changes.

Scientific Applications:

• Protein–Protein Interaction Mapping: Elucidates principles of PPIs by identifying energetic hotspot residues and their contributions to binding.
• Mutational Impact Prediction: Predicts how specific amino acid substitutions alter binding free energy to support studies of mutational effects.
• Therapeutic Design: Guides design and prioritization of therapeutics targeting protein–protein interfaces by identifying critical interface residues and mutations.

Methodology:

Computational alanine scanning, exhaustive mutation scanning, molecular dynamics simulations, and one-step free energy perturbation are used to compute binding free energy changes.