In those cases, conformation changes of the fusogen, usually helical bundle zippering, drive the fusion reaction.
The impact of receptors bearing the highest AUROC values during the model selection step (conformation 4 and 19 for D3R and M2R templates, respectively) proves that the performance of individual homology models has little influence on the obtained results and, in some cases (conformation 19 based on M2R in screening against ZINC subset – Figure 2c), can even lower VS performance.
In such cases, conformation may be acquired by DNA- and protein partner-binding and such interactions may account for domain-specific requirements.
In many cases, conformations generated by enhanced sampling methods such as TAMD were in good agreement with crystallographic, NMR, and low-resolution EM data.
In each case, the conformation of the most favorable estimated energy is used as the predicted conformation.
ST conditions, on the other hand, prevail when the interaction with the surface is strong enough to prevent an adsorbed part of the molecule from moving further; in that case, the conformation on the surface is close to a two-dimensional projection of the three-dimensional solution conformation.
However, in this case, closed conformation was formed by A272/G273 bulged-in and A272*/G273* bulged-out stacks (Fig. 4).
In these two cases, the conformation of the ligand in the solid state has been defined in detail by a crystal structure determination.
As is often the case, borderline conformations are observed and are difficult to eliminate but do not alter the inferred landscape.
In several cases, three conformations of RF groups generated by rotation of perfluoroalkyl C C bonds had to be included in the final refined model.
