Gene regulation is very complex, but since DNA provides a one-dimensional template for protein binding, most events can be described with one-dimensional lattice models. 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).
Below is an annotated list of online resources where the parameters may be obtained for calculations
Protein-DNA binding databases (thermodynamics & weight matrices):
The JASPAR CORE database contains a curated, non-redundant set of profiles, derived from published collections of experimentally defined transcription factor binding sites for eukaryotes. The prime difference from TRANSFAC is the open data acess.
KDBI is a collection of experimentally determined kinetic data of protein-protein, protein-RNA, protein-DNA, protein-ligand, RNA-ligand, DNA-ligand binding events described in the literature. Currently, KDBI contains 19,263 records. (Feb 2010).
ProNIT currently contains more than 4900 entries. Each entry has the protein and nucleic acid information, experimental conditions and the following binding thermodynamic data: dissociation constant Kd, energies, stoichiometry of binding and activity (Km and kcat).
UniPROBE contains data on the preferences of proteins for all possible sequence variants ('words') of length k ('k-mers'), as well as position weight matrix (PWM) and graphical sequence logo representations of the k-mer data. In total, the database currently hosts DNA binding data for 391 nonredundant proteins (individual proteins or in some cases heterodimers) from a diverse collection of organisms.
TRANSFAC consists of free and paid sections. I did nto check the paid section. Human TF weight matrices may be viewed through the web interface of UCSC Genome Browser. Provided binding sites are experimentally proved.
In eukaryotes, the wrapping of DNA around the histone octamer complex has long been recognized as a mechanism to regulate DNA access for other proteins. Nucleosome positions are determined by three major contributions: the intrinsic binding affinity of the histone octamer depends on the DNA sequence, competitive/cooperative binding of other protein factors, and active translocation by ATP-dependent remodeling complexes. The challenge is to take into accout all these contributions and predict nucleosome repositioning in gene regulation in vivo (
