Quality matters: extension of clusters of residues with good hydrophobic contacts stabilize (hyper)thermophilic proteins.
Identifying determinant(s) of protein thermostability is key for rational and data-driven protein engineering. By analyzing more than 130 pairs of mesophilic/(hyper)thermophilic proteins, we identified the quality (residue-wise energy) of hydrophobic interactions as a key factor for protein thermostability. This distinguishes our study from previous ones that investigated predominantly structural determinants. Considering this key factor, we successfully discriminated between pairs of mesophilic/(hyper)thermophilic proteins (discrimination accuracy: ∼80%) and searched for structural weak spots in E. coli dihydrofolate reductase (classification accuracy: 70%).
Institute for Pharmaceutical and Medicinal Chemistry, Department of Mathematics and Natural Sciences, Heinrich Heine University , Universitätsstr. 1, 40225 Düsseldorf, Germany.
Prakash Chandra
PC
Rathi
Hans Wolfgang
HW
Höffken
Holger
H
Gohlke
D004926:Escherichia coli / Q000201:enzymology; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011487:Protein Conformation; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry*; D013696:Temperature; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry
D011506:Proteins; D013762:Tetrahydrofolate Dehydrogenase