title: Computational design of protein-ligand interfaces: potential in therapeutic development.
abstract: 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.
authors.affiliation: Departments of Chemistry, Pharmacology, and Biomedical Informatics, Vanderbilt University, 7330 Stevenson Center, Station B 351822, Nashville, TN 37235, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Morin
authors.forename: Jens
authors.initials: J
authors.lastname: Meiler
authors.forename: Laura S
authors.initials: LS
authors.lastname: Mizoue
mesh_terms: D001665:Binding Sites; D019295:Computational Biology; D055808:Drug Discovery; D008024:Ligands; D011485:Protein Binding; D015202:Protein Engineering; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D011506:Proteins