BROMODOMAINS PROTEINS

Bromodomains (BRDs) are evolutionarily conserved protein-protein interaction modules that are found in a wide range of proteins with diverse catalytic and scaffolding functions and are present in most tissues. Bromodomain and extra-terminal (BET) proteins orchestrate a multitude of transcriptional networks through their interactions with acetylated and nonacetylated binding partners. BRD-containing proteins are frequently dysregulated in cancer, they participate in gene fusions that generate diverse, frequently oncogenic proteins, and many cancer-causing mutations have been mapped to the BRDs themselves.

Computational Development of BRD Inhibitors/Ligands

Bromodomains have been viewed as therapeutically important targets. Structural analysis data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family. Subsequent progress in the development of drug-like bromodomain ligands has been rapid via in silico approaches. Proteochemometric (PCM) can be applied to future virtual screening and compound design, including an off-target prediction for bromodomains.

The 61 BRDs in the human genome cluster into several families based on structure/sequence similarity. Here, CD ComputaBio presents high-resolution crystal structures, covering the main BRD families, for computational research applications.