PocketOptimizer and the Design of Ligand Binding Sites
PocketOptimizer is a computational method to design protein binding pockets that has been recently developed. Starting from a protein structure an existing small molecule binding pocket is optimized for the recognition of a new ligand. The modular program predicts mutations that will improve the affinity of a target small molecule to the protein of interest using a receptor–ligand scoring function to estimate the binding free energy. PocketOptimizer has been tested in a comprehensive benchmark and predicted mutations have also been used in experimental tests. In this chapter, we will provide general recommendations for usage as well as an in-depth description of all individual PocketOptimizer modules.
Key wordsComputational protein design Protein–small molecule interaction Ligand binding design Enzyme engineering PocketOptimizer
Financial support from the German Research Foundation (DFG grant HO 4022/2-3) is acknowledged. M.N. was supported by the Erasmus+ mobility program. The authors like to thank Steffen Schmidt for comments on the manuscript.
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