Determining thermodynamic properties of molecular interactions from single crystal studies.
The concept of single crystals of macromolecules as thermodynamic systems is not a common one. However, it should be possible to derive thermodynamic properties from single crystal structures, if the process of crystallization follows thermodynamic rules. We review here an example of how the stabilizing potentials of molecular interactions can be measured from studying the properties of DNA crystals. In this example, we describe an assay based on the four-stranded DNA junction to determine the stabilizing potentials of halogen bonds, a class of electrostatic interactions, analogous to hydrogen bonds, that are becoming increasing recognized as important for conferring specificity in protein-ligand complexes. The system demonstrates how crystallographic studies, when coupled with calorimetric methods, allow the geometries at the atomic level to be directly correlated with the stabilizing energies of molecular interactions. The approach can be generally applied to study the effects of DNA sequence and modifications of the thermodynamic stability of the Holliday junction and, by inference, on recombination and recombination dependent processes.
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870, United States(1)Current address: Department of Biochemistry and Biophysics, Stockholm Univeristy SE-106 91 Stockholm, Sweden.
Crystal M
CM
Vander Zanden
Megan
M
Carter
Pui Shing
PS
Ho
D002151:Calorimetry / Q000379:methods; D003461:Crystallography / Q000379:methods*; D004247:DNA / Q000737:chemistry*; D045566:DNA, Cruciform / Q000737:chemistry; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011995:Recombination, Genetic; D013816:Thermodynamics
D045566:DNA, Cruciform; D004247:DNA
Br; Cl; DNA structure and stability; DSC; F; H-bond; Halogen bonds; I; IsoH; IsoX; N; Pu; Py; SAS; SFE; X-bond; bromine; chlorine; differential scanning calorimetry; fluorine; halogen bond; halogen bonded isomer; hydrogen bond; hydrogen bonded isomer; iodine; nucleotide; purine; pyrimidine; solvent accessible surface; solvent free energy