Bioinformatic method for protein thermal stabilization by structural entropy optimization.
Engineering proteins for higher thermal stability is an important and difficult challenge. We describe a bioinformatic method incorporating sequence alignments to redesign proteins to be more stable through optimization of local structural entropy. Using this method, improved configurational entropy (ICE), we were able to design more stable variants of a mesophilic adenylate kinase with only the sequence information of one psychrophilic homologue. The redesigned proteins display considerable increases in their thermal stabilities while still retaining catalytic activity. ICE does not require a three-dimensional structure or a large number of homologous sequences, indicating a broad applicability of this method. Our results also highlight the importance of entropy in the stability of protein structures.
Bae
Euiyoung
E
Departments of Biochemistry and Computer Science, University of Wisconsin, Madison, WI 53706, USA.
Bannen
Ryan M
RM
Phillips
George N
GN
D000263:Adenylate Kinase / Q000737:chemistry; D019295:Computational Biology / Q000379:methods*; D019277:Entropy; D011487:Protein Conformation; D011489:Protein Denaturation; D015202:Protein Engineering / Q000379:methods; D011506:Proteins / Q000737:chemistry*; D013696:Temperature
D011506:Proteins; D000263:Adenylate Kinase