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How to Stabilize Protein: Stability Screens for Thermal Shift Assays and Nano Differential Scanning Fluorimetry in the Virus-X Project
Published on: February 11, 2019
Hydrophobicity density profiles to predict thermal stability enhancement in proteins
Angel Mozo-Villarías1, Juan Cedano, Enrique Querol
1Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, 25198, Lleida, Spain. angel.mozo@cmb.udl.es
Abstract:
A hydrophobicity density is defined for a protein through its hydrophobicity tensor (similar to the inertia tensor), by using the Eisenberg hydrophobicity scale of the hydrophobic amino acids of a protein. This allows calculation of the radii of the corresponding hydrophobic ellipsoid of a protein and thus subsequently of its hydrophobic density. A hydrophobicity density profile is then obtained by simulating point mutations of each amino acid of a protein either to a high hydrophobicity value or to zero hydrophobicity. It is found that an increase in the hydrophobic density of the protein correlates with an increase of its mid-point transition temperature. From this profile it is possible to determine the amino acids or domain stretches in a protein that are most amenable to mutation in order to increase the thermal stability. The model is tested to predict the thermostabilisation effects of two mutations in a beta-glucanase: M29G and M29F. This model is compared with other hydrophobicity-related profiles described by other authors.
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