Rapid prediction of crucial hotspot interactions for icosahedral viral capsid self-assembly by energy landscape atlasing validated by mutagenesis
Fig 5
Prediction using cruciality bar-codes described in the section on interaction cruciality for two VP monomers assembling across a hexamer interface in BMV.
Each node in the atlas roadmap in the middle represents an active constraint region (macrostate) in EASAL. Example active constraint graphs are shown at far left: the yellow and red circles represent atoms participating in active constraints (interactions) in the two VP monomers. At each successive level, the number of active constraints increases by 1 and the energy level and effective dimension decrease by 1. The atlas nodes in the bottom-most row represent the 0-dimensional, lowest energy, stable assembly configurations; example configurations shown below them. Their total number (for a given interface s, on removal of a given interaction or constraint r) gives in the computation of the cruciality bar-code. Each such configuration together with nearby higher-energy configurations in all of their ancestor nodes constitute one potential energy basin. Their sum, across all basins, weighted by energy level gives the denominator of
. The rightmost of the stable assembly configurations at the bottom corresponds to the true realization. Above it, the 3 solid configurations and the transparent sweeps around them show the closest configurations to the true realization in successively higher energy regions in its basin (one region each for 3 energy levels shown). To the far left, these sweeps are shown as orange highlights in the corresponding Cayley parameterized regions. The colorful basin plot shows the total weighted configurations in the true basin, stratified by dimension or energy level. Their sum is the numerator of
.