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What is Interface Alanine Scanning?

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What is Interface Alanine Scanning?

    Interface Alanine Scanning attempts to estimate the energetic contribution to the binding free energy provided by each residue at a protein-protein interface. Briefly, interface alanine scanning uses a simple physical model to score a series of protein-protein interfaces in which contact residues are individually replaced with alanine. After each computational alanine mutation, the resulting binding energy is calculated.

    The input consists of a three-dimensional structure of a protein-protein complex; output is a list of "hot spots," or amino acid side chains that are predicted to significantly destabilize the interface when mutated to alanine, analogous to the results of experimental alanine-scanning mutagenesis. 79% of hot spots and 68% of neutral residues were correctly predicted in a test of 233 mutations in 19 protein-protein complexes. A single interface can be analyzed in minutes. The computational methodology has been validated by the successful design of protein interfaces with new specificity and activity and has yielded new insights into the mechanisms of receptor specificity and promiscuity in biological systems.

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