outcome of adaptation to its task as a decoder or the result of other constraints. Recent study derived the energy landscape that provides optimal discrimination between competing tRNA substrates, and thereby optimal tRNA decoding. The optimal landscape is a symmetric one (see image). The study shows that the measured landscape of the prokaryotic ribosome is indeed symmetric. This model suggests that conformational changes of the ribosome and tRNA during decoding are means to obtain such an optimal tRNA decoder. The fact that both homologous recombination and tRNA decoding utilize conformational proofreading suggests that this is a generic mechanism that may be utilized broadly by molecular recognition systems. In other biological systems Human UV-damage repair A recent study shows that conformational proofreading is used by human DNA repair mechanisms. The research focused on the question of how DNA-repair proteins scan the human genome for UV-induced damage during the initial step of nucleotide excision repair (NER). Detailed single-molecule measurements revealed how the human UV-damaged DNA-binding protein (UV-DDB) performs a 3D search. The authors find that "UV-DDB examines sites on DNA in discrete steps before forming long-lived, nonmotile UV-DDB dimers (DDB1-DDB2)2 at sites of damage. Analysis of the rates of dissociation for the transient binding molecules on both undamaged and damaged DNA show multiple dwell times over three orders of magnitude... These intermediate states are believed to represent discrete UV-DDB conformers on the trajectory to stable damage detection." The authors conclude from their detailed kinetic measurements that UV-DDB recognizes lesions using a conformational proofreading mechanism via multiple intermediates. Other recognition schemes Relation to kinetic proofreading In the kinetic proofreading schema, a time delay (equivalently, an irreversible intermediate stage) is introduced during the formation of the correct or incorrect complexes. This time delay reduces the production rates of both complexes but enhances the fidelity beyond the equilibrium limit. The irreversibility of the scheme requires an energy source. The time delay in kinetic proofreading is analogous to the spatial difference in conformational proofreading. However, the conformational proofreading can be an equilibrium scheme that does not consume energy. References External links Related articles Mathematical and theoretical biology Biomolecules Enzymes