Proteus and the design of ligand binding sites
Archontis, Georgios Z.
SourceMethods in Molecular Biology
Google Scholar check
MetadataShow full item record
This chapter describes the organization and use of Proteus, a multitool computational suite for the optimization of protein and ligand conformations and sequences, and the calculation of pKα shifts and relative binding affinities. The software offers the use of several molecular mechanics force fields and solvent models, including two generalized Born variants, and a large range of scoring functions, which can combine protein stability, ligand affinity, and ligand specificity terms, for positive and negative design. We present in detail the steps for structure preparation, system setup, construction of the interaction energy matrix, protein sequence and structure optimizations, pKα calculations, and ligand titration calculations. We discuss illustrative examples, including the chemical/structural optimization of a complex between the MHC class II protein HLA-DQ8 and the vinculin epitope, and the chemical optimization of the compstatin analog Ac-Val4Trp/His9Ala, which regulates the function of protein C3 of the complement system. © Springer Science+Business Media New York 2016.
Showing items related by title, author, creator and subject.
Computational protein design with a generalized born solvent model: Application to asparaginyl-tRNA synthetase Polydorides, Savvas; Amara, Najette; Aubard, C.; Plateau, P.; Simonson, T.; Archontis, Georgios Z. (2011)Computational Protein Design (CPD) is a promising method for high throughput protein and ligand mutagenesis. Recently, we developed a CPD method that used a polar-hydrogen energy function for protein interactions and a ...
Pitsouli, Chrysoula; Delidakis, Christos (2005)Lateral inhibition is a pattern refining process that generates single neural precursors from a field of equipotent cells and is mediated via Notch signaling. Of the two Notch ligands Delta and Serrate, only the former was ...
Two ligand-binding sites in the O2-sensing signal transducer HemAT: Implications for ligand recognition/discrimination and signaling Pinakoulaki, Eftychia; Yoshimura, H.; Daskalakis, Vangelis; Yoshioka, S.; Aono, S.; Varotsis, Constantinos (2006)We have identified a ligand (CO) accommodation cavity in the signal transducer sensor protein HemAT (heme-based aerotactic transducer) that allows us to gain single-molecule insights into the mechanism of gas sensor proteins. ...