Breaking the conformational ensemble barrier: Ensemble structure
modeling challenges in CASP15
Abstract
For the first time, the 2022 CASP (Critical Assessment of Structure
Prediction) community experiment included a section on computing
multiple conformations for protein and RNA structures. There was full or
partial success in reproducing the ensembles for four of the nine
targets, an encouraging result. For protein structures, enhanced
sampling with variations of the AlphaFold2 deep learning method was by
far the most effective approach. One substantial conformational change
caused by a single mutation across a complex interface was accurately
reproduced. In two other assembly modeling cases, methods succeeded in
sampling conformations near to the experimental ones even though
environmental factors were not included in the calculations. An
experimentally derived flexibility ensemble allowed a single accurate
RNA structure model to be identified. Difficulties included how to
handle sparse or low-resolution experimental data and the current lack
of effective methods for modeling RNA/protein complexes. However, these
and other obstacles appear addressable.