Journal article
Computational Design of the Tiam1 PDZ Domain and Its Ligand Binding
Journal of chemical theory and computation, Vol.13(5), pp.2271-2289
04/25/2017
DOI: 10.1021/acs.jctc.6b01255
PMID: 28394603
Abstract
PDZ domains direct protein-protein interactions and serve as models for protein design. Here, we optimized a protein design energy function for the Tiam1 and Cask PDZ domains that combines a molecular mechanics energy, Generalized Born solvent, and an empirical unfolded state model. Designed sequences were recognized as PDZ domains by the Superfamily fold recognition tool and had similarity scores comparable to natural PDZ sequences. The optimized model was used to redesign the two PDZ domains, by gradually varying the chemical potential of hydrophobic amino acids; the tendency of each position to lose or gain a hydrophobic character represents a novel hydrophobicity index. We also redesigned four positions in the Tiam1 PDZ domain involved in peptide binding specificity. The calculated affinity differences between designed variants reproduced experimental data and suggest substitutions with altered specificities.
Details
- Title: Subtitle
- Computational Design of the Tiam1 PDZ Domain and Its Ligand Binding
- Creators
- David Mignon - Laboratoire de Biochimie de l'Ecole polytechniqueNicolas Panel - Laboratoire de Biochimie de l'Ecole polytechniqueXingyu Chen - Laboratoire de Biochimie de l'Ecole polytechniqueErnesto Fuentes - University of Iowa [Iowa City]Thomas Simonson - Laboratoire de Biochimie de l'Ecole polytechnique
- Resource Type
- Journal article
- Publication Details
- Journal of chemical theory and computation, Vol.13(5), pp.2271-2289
- DOI
- 10.1021/acs.jctc.6b01255
- PMID
- 28394603
- NLM abbreviation
- J Chem Theory Comput
- ISSN
- 1549-9618
- eISSN
- 1549-9626
- Publisher
- American Chemical Society
- Language
- English
- Date published
- 04/25/2017
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9984025275502771
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