Predicting the effects o f basepai r mutatio ns in proline-rich h omeodomain (PRH)-DNA complex by thermodynamic integration

The PRH (Prolin e-Rich Hom eodomain) protein [۱] is a DNA b inding protein having a key role i n the regulation of gene expression in all eukaryotes. All types of the homeodo mains intera ct with its conserved ۵' -TAATNN- ۳' binding sequence. Ho meodomain s with glut amine at position ۵۰, li ke PRH, re cognize TAATTG, TA ATTA or TAATGG sites. The co mplex between PRH and TAATTG were consid ered as a native complex. With m utation of the GC and TA base pairs in TAATTG to AT and GC, respectively, two mutated complexes (M۱ and M۲ c omplexes) w ere created. To predict of the effe cts of basepair mutations in PRH-DNA complexes, the binding free energy c hanges in each of t wo created mutations were investigated.

کلیدواژه ها:

proline-rich home odomian ، M D simulatio ns ، Free en ergy ، bindin g affinity