TY - JOUR T1 - Active Nuclear Receptors Exhibit Highly Correlated AF-2 Domain Motions A1 - Teotico, Denise G. A1 - Frazier, Monica L. A1 - Ding, Feng A1 - Dokholyan, Nikolay V. A1 - Temple, Brenda R. S. A1 - Redinbo, Matthew R. Y1 - 2008/07/11 N2 - Author SummaryLong-range motions play essential roles in protein function but are difficult to appreciate from static crystal structures. We sought to understand how macromolecular motion affects the formation of transcriptional complexes central to controlling gene expression. Using 20- to 30-ns molecular dynamics simulations, we examined three nuclear receptors that function as ligand-regulated transcription factors: the pregnane X receptor, the peroxisome proliferator-activator receptor-γ, and estrogen receptor-α. We found that each of these receptors exhibits a high degree of correlated motions within the domain responsible for forming functionally essential protein–protein interactions with transcriptional coactivators. We further found that specific long-range (up to 30 Å) motions play an important role in these dynamics. Our results show that “active-capable” nuclear receptors are prepared for coactivator contacts by maintaining a mobile but preformed protein–protein interaction surface. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 4 IS - 7 UR - https://doi.org/10.1371/journal.pcbi.1000111 SP - e1000111 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1000111 ER -