pKa's of ionizable groups and energetics of protein conformational transitions.
It is well-known that the stability of proteins is pH-dependent because proteins contain groups capable of exchanging protons with their environment. In general, all conformational transitions of proteins might be expected to exhibit some pH-dependence. Using structural data for folded and partially unfolded forms of the Drosophila melanogaster engrailed homeodomain, we show that knowledge of the pK(a)'s of ionizable groups in different structural forms of a protein is not sufficient to determine pH-dependence of the free energy of its conformational transitions with accuracy better than 1 kcal/mol. We also describe a convenient computational approach for predicting expected errors when free energy of conformational transition is derived exclusively from the pK(a) values. This approach uses the full interaction free energy matrix between the ionizable sites, for the two forms of the protein, which can be determined when appropriate structural information is available.
Piłat
Zofia
Z
Division of Biophysics, Institute of Experimental Physics, Department of Physics, University of Warsaw Zwirki i Wigury 93 Street, Warsaw 02-089, Poland.
Antosiewicz
Jan M
JM
D000595:Amino Acid Sequence; D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055585:Physical Phenomena; D011487:Protein Conformation; D011489:Protein Denaturation; D013696:Temperature; D013816:Thermodynamics
D029721:Drosophila Proteins