ISSN:
0948-5023
Schlagwort(e):
Keywords Hydrogen Bonds
;
Protein-DNA Binding
;
Specificity
;
Water
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Chemie und Pharmazie
Notizen:
Abstract We extend our previous analysis of binding specificity of DNA-protein complexes to complexes containing water-mediated bridges. Inclusion of water bridges between phosphate and base, phosphate and sugar, as well as proteins and DNA, improves the prediction of specificity; six data sets studied in this paper yield correct predictions for all base pairs that have two or more hydrogen-bonds. Beside massive computation, our approach relies highly on experimental data. After deriving protein structures from DNA-protein complexes in which coordinates were established by X-ray diffraction techniques, we analysed all possible DNA sequences to which these proteins might bind, ranking them in terms of Lennard-Jones potential for the optimal docking configuration. Our prediction algorithm rests on the following assumptions: (1) specificity comes mainly from direct hydrogen bonding; (2) electrostatic forces stabilise DNA-protein complexes and contribute only weakly to specificity since they occur at the charged phosphate groups; (3) Van der Waals forces and electrostatic interactions between positively charged groups on the protein and phosphates on DNA can be neglected as they contribute primarily to the free energy of stabilisation as opposed to specificity.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/s008940050121
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