Towards computational specificity screening of DNA-binding proteins.

ABSTRACT: DNA-binding proteins are key players in the regulation of gene expression and, hence, are essential for cell function. Chimeric proteins composed of DNA-binding domains and DNA modifying domains allow for precise genome manipulation. A key prerequisite is the specific recognition of a particular nucleotide sequence. Here, we quantitatively assess the binding affinity of DNA-binding proteins by molecular dynamics-based alchemical free energy simulations. A computational framework was developed to automatically set up in silico screening assays and estimate free energy differences using two independent procedures, based on equilibrium and non-equlibrium transformation pathways. The influence of simulation times on the accuracy of both procedures is presented. The binding specificity of a zin

SUBMITTER: Seeliger D 

PROVIDER: S-EPMC3201868 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature