Experimentally based contact energies decode interactions responsible for protein-DNA affinity and the role of molecular waters at the binding interface.

ABSTRACT: A major obstacle towards understanding the molecular basis of transcriptional regulation is the lack of a recognition code for protein-DNA interactions. Using high-quality crystal structures and binding data on the promiscuous family of C(2)H(2) zinc fingers (ZF), we decode 10 fundamental specific interactions responsible for protein-DNA recognition. The interactions include five hydrogen bond types, three atomic desolvation penalties, a favorable non-polar energy, and a novel water accessibility factor. We apply this code to three large datasets containing a total of 89 C(2)H(2) transcription factor (TF) mutants on the three ZFs of EGR. Guided by molecular dynamics simulations of individual ZFs, we map the interactions into homology models that embody all feasible intra- and intermolecula

SUBMITTER: Temiz NA 

PROVIDER: S-EPMC2709573 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature