2022
DOI: 10.3389/fbioe.2022.838129
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Molecular dynamics identifies semi-rigid domains in the PD-1 checkpoint receptor bound to its natural ligand PD-L1

Abstract: Cells in danger of being erroneously attacked by leucocytes express PD-L1 on their surface. These cells activate PD-1 on attacking leucocytes and send them to death, thus curbing erroneous, autoimmune attack. Unfortunately, cancer cells exploit this mechanism: By expressing PD-L1, they guard themselves against leucocyte attack and thereby evade immune clearance. Checkpoint inhibitors are drugs which re-enable immune clearance of cancer cells by blocking the binding of PD-L1 to PD-1 receptors. It is therefore o… Show more

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Cited by 2 publications
(3 citation statements)
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References 43 publications
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“…The PD-1/PD-L1 adduct was also investigated by Kenn et al [ 66 ] performing MD simulations (three replicas of 600 ns) using the Amber99sb-ildn FF coupling with an unsupervised clustering method. They identified specific regions of the PD-1/PD-L1 complex forming stable clusters over time, which are hence named “semi-rigid domains”.…”
Section: Computational Studies Contributing To the Binding Mechanism ...mentioning
confidence: 99%
“…The PD-1/PD-L1 adduct was also investigated by Kenn et al [ 66 ] performing MD simulations (three replicas of 600 ns) using the Amber99sb-ildn FF coupling with an unsupervised clustering method. They identified specific regions of the PD-1/PD-L1 complex forming stable clusters over time, which are hence named “semi-rigid domains”.…”
Section: Computational Studies Contributing To the Binding Mechanism ...mentioning
confidence: 99%
“…The right part of panel C shows the molecule rotated. (Images partly taken from [8] and [5] with permission). …”
Section: Introductionmentioning
confidence: 99%
“…This mechanism can also be blocked by modern drugs, immune-checkpoint-inhibitors, such as Pembrolizumab or Nivolumab. In previous work we have investigated their molecular action in detail [4] , [5] , [6] , [7] , [8] . Checkpoint-inhibitors are pharmacologically designed to bind to PD-1 without activating it.…”
Section: Introductionmentioning
confidence: 99%