Hydrophobicity density profiles to predict thermal stability enhancement in proteins.
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.
Mozo-Villarías
Angel
A
Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, 25198, Lleida, Spain. angel.mozo@cmb.udl.es
Cedano
Juan
J
Querol
Enrique
E
D044602:Cellulases / Q000737:chemistry; D004560:Electricity; D004795:Enzyme Stability; D006358:Hot Temperature; D057927:Hydrophobic and Hydrophilic Interactions; D016014:Linear Models; D008956:Models, Chemical; D009154:Mutation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D013696:Temperature
D011506:Proteins; D044602:Cellulases