Computational design of protein-ligand interfaces: potential in therapeutic development.

Morin A, Meiler J, Mizoue LS
Trends Biotechnol. 2011 29 (4): 159-66

PMID: 21295366 · PMCID: PMC3749302 · DOI:10.1016/j.tibtech.2011.01.002

Computational design of protein-ligand interfaces finds optimal amino acid sequences within a small-molecule binding site of a protein for tight binding of a specific small molecule. It requires a search algorithm that can rapidly sample the vast sequence and conformational space, and a scoring function that can identify low energy designs. This review focuses on recent advances in computational design methods and their application to protein-small molecule binding sites. Strategies for increasing affinity, altering specificity, creating broad-spectrum binding, and building novel enzymes from scratch are described. Future prospects for applications in drug development are discussed, including limitations that will need to be overcome to achieve computational design of protein therapeutics with novel modes of action.

Copyright © 2011 Elsevier Ltd. All rights reserved.

MeSH Terms (8)

Binding Sites Computational Biology Drug Discovery Ligands Protein Binding Protein Engineering Proteins Protein Stability

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