Knob-Socket Model: A novel method of predicting protein stability - CORE CORE Search Search Services Access to raw data API Dataset FastSync Content discovery Recommender Discovery Managing content Repository dashboard Support FAQs About About CORE Blog Contact us Knob-Socket Model: A novel method of predicting protein stability By Joshman Raj Singh, Bianca Nguyen, Huy Pham, Isabelle Huynh and Danielle MacArt Abstract The Tsai laboratory developed a novel description of protein tertiary packing called the Knob-Socket Model. This model describes protein packing at the tertiary and quaternary levels of protein structure as involving a four-residue tetrahedral motif. The motif consists of a three-amino acid socket from one piece of a secondary structure that can be packed by a single amino acid knob from another piece of a secondary structure. A protein a-helix, named KSα1.1, was designed to validate the Knob-Socket Model, using the packing code derived by the Protein Data Bank. To computationally predict the packing of peptide chains, propensity libraries were used based on the amino acid composition of the knob-socket motif from these known secondary structures. So, the amino acid composition of sockets favors or disfavors a-helical formation. These a-helical propensity libraries were used to design KSα1.1, and also predict the effect of point mutations on the KSα1.1 structure. So, the KSα1.1 mutants were classified as having a potentially higher or lower a-helical character in comparison to the wild-type protein. Corresponding point mutant variants of the KSα1.1 protein were created through site-directed mutagenesis. Using circular dichroism (CD) analysis, the a-helicity of the mutant proteins were characterized. The a-helical character of the mutated proteins in comparison to the wild type KSα1.1 were then compared to the original prediction made from the propensity library. Using raw data collected from the CD graphs, deconvolution studies were conducted through different protein analysis programs in order to quantify and calculate the KSα1.1 a-helical content of each mutant. Additionally, an increase of the a-helical character of a protein indicates a more stable structure in comparison to the wild type protein. To further determine structural stability, proteins were placed through both chemical and thermal denaturation studies. The future aims of this project include creating, analyzing, and characterizing proteins with double mutations Topics: Biochemistry Publisher: Scholarly Commons Year: 2018 OAI identifier: oai:scholarlycommons.pacific.edu:purcc-1261 Provided by: Scholarly Commons Download PDF: Sorry, we are unable to provide the full text but you may find it at the following location(s): https://scholarlycommons.pacif... (external link) Suggested articles To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request. Useful links Blog Services About CORE Contact us Cookies Privacy notice Writing about CORE? Discover our research outputs and cite our work. CORE is a not-for-profit service delivered by the Open University and Jisc.
