When theory meets experiment: the PD-1 challenge
Applying atomistic computational modeling to drug discovery has proven to be a hugely successful approach, allowing drug–receptor interactions to be predicted and drugs to be optimized for potency, selectivity, and safety. However, when it comes to predicting protein–protein interactions and to rationally designing regulators of these interactions, computational tools often fail. Here, we report one of the rare instances where state-of-the-art computer simulations, guided by experiment, were able to correctly predict one of the most sophisticated protein–protein interactions. We revisit our previous discovery of the complex of human PD-1 with the ligand PD-L1 and compare our earlier findings with the recently published crystal structure of the same complex. Side-by-side comparison of the model of the complex with its crystal structure reveals outstanding agreement and suggests that our protein–protein prediction workflow could be applied to similar problems.
Publisher URL: https://link.springer.com/article/10.1007/s00894-017-3482-x
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