Simulating structural transitions during protein-DNA recognition

Abstract

DNA-binding proteins specifically bind certain DNA sequences after scanning through millions of base pairs. During the nonspecific exploration the interactions between protein and DNA constantly form and break on the timescale of microseconds. Specific interactions at the target sites, on the other hand, are stable for seconds. The speed accuracy trade-off leads to the frequent target site missing observed in the case of our model system, the transcription factor LacI. Here, we study the conformational landscape of the dimeric LacI and a number of operator sequences during nonspecific and specific interaction to investigate how the transcription factor optimises fast search (<4 min) and strong specific binding (<10−9 M).