Greet De Baets1, Joost Van Durme1, Rob van der Kant2, Joost Schymkowitz2, Frederic Rousseau2. 1. VIB Switch Laboratory, Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven, 3000 Leuven, Belgium and Vrije Universiteit Brussel, 1050 Brussels, Belgium. 2. VIB Switch Laboratory, Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven, 3000 Leuven, Belgium and.
Abstract
MOTIVATION: Protein aggregation is associated with a number of protein misfolding diseases and is a major concern for therapeutic proteins. Aggregation is caused by the presence of aggregation-prone regions (APRs) in the amino acid sequence of the protein. The lower the aggregation propensity of APRs and the better they are protected by native interactions within the folded structure of the protein, the more aggregation is prevented. Therefore, both the local thermodynamic stability of APRs in the native structure and their intrinsic aggregation propensity are a key parameter that needs to be optimized to prevent protein aggregation. RESULTS: The Solubis method presented here automates the process of carefully selecting point mutations that minimize the intrinsic aggregation propensity while improving local protein stability.
MOTIVATION:Protein aggregation is associated with a number of protein misfolding diseases and is a major concern for therapeutic proteins. Aggregation is caused by the presence of aggregation-prone regions (APRs) in the amino acid sequence of the protein. The lower the aggregation propensity of APRs and the better they are protected by native interactions within the folded structure of the protein, the more aggregation is prevented. Therefore, both the local thermodynamic stability of APRs in the native structure and their intrinsic aggregation propensity are a key parameter that needs to be optimized to prevent protein aggregation. RESULTS: The Solubis method presented here automates the process of carefully selecting point mutations that minimize the intrinsic aggregation propensity while improving local protein stability.
Authors: Katerina C Nastou; Eleftheria G Karataraki; Nikos C Papandreou; Anna-Isavella G Rerra; Vassiliki P Grimanelli; Ilias Maglogiannis; Stavros J Hamodrakas; Vassiliki A Iconomidou Journal: Adv Exp Med Biol Date: 2020 Impact factor: 2.622
Authors: Sandeep Kumar; A Mary Thangakani; R Nagarajan; Satish K Singh; D Velmurugan; M Michael Gromiha Journal: Sci Rep Date: 2016-02-29 Impact factor: 4.379