Although binding events are very complex, gene regulation is still centered on the DNA or RNA, which provides a one-dimensional template for protein binding. The general idea behind one-dimensional lattice models is that the DNA is divided into the elementary units and described by multiple states associated with each of the unit (bound/unbound). The elementary DNA units are usually taken as nucleotides (A, T, G, C) or base pairs. Basic features of DNA-protein-drug binding encountered in gene regulation include site specificity determined by the DNA sequence; binding site overlapping; competitions between different protein types or different binding modes; interactions between proteins bound to the DNA; multilayer binding (when a protein bound to the DNA presents a lattice for the next-layer binding of other proteins), and protein-assisted DNA looping (Teif, NAR 2007; Teif, BJ 2010). In chromatin, additional complex elements such as nucleosomes, remodelers and higher-order chromatin structures should be taken into account (Teif and Rippe, NAR 2009; Teif and Rippe, JPCM 2010; Teif et al., BJ 2010).