ArticleCell communication and signaling : CCS2018
The design of high affinity human PD-1 mutants by using molecular dynamics simulations (MD).
Article in Cell communication and signaling : CCS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 33 citations in OpenAlex.
- The impact of PD-1 mutations on pembrolizumab binding: insights from molecular dynamics and MM-GBSA analysis.Scientific reports · 2026Article
- Small molecules targeting the PD-1/PD-L1 axis for cancer immunotherapy.Theranostics · 2026Review
- PD-1 is conserved from sharks to humans: new insights into PD-1, PD-L1, PD-L2, and SHP-2 evolution.Frontiers in immunology · 2025Article
- A Comprehensive Computational Insight into the PD-L1 Binding to PD-1 and Small Molecules.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Structural Insights of PD-1/PD-L1 Axis: AnCurrent protein & peptide science · 2024Article
- Recent Advances in Nanoparticles-Based Platforms Targeting the PD-1/PD-L1 Pathway for Cancer Treatment.Pharmaceutics · 2022Review
- Molecular Mechanism of Food-Derived Polyphenols on PD-L1 Dimerization: A Molecular Dynamics Simulation Study.International journal of molecular sciences · 2021Article
- Molecular Mechanism of Small-Molecule Inhibitors in Blocking the PD-1/PD-L1 Pathway through PD-L1 Dimerization.International journal of molecular sciences · 2021Article
- Computer-aided design of PVR mutants with enhanced binding affinity to TIGIT.Cell communication and signaling : CCS · 2021Article
- Dynamics of binding ability prediction between spike protein and human ACE2 reveals the adaptive strategy of SARS-CoV-2 in humans.Scientific reports · 2021Article
- Modeling the MreB-CbtA Interaction to Facilitate the Prediction and Design of Candidate Antibacterial Peptides.Frontiers in molecular biosciences · 2021Article
- Article
- Molecular dynamics of the immune checkpoint programmed cell death protein I, PD-1: conformational changes of the BC-loop upon binding of the ligand PD-L1 and the monoclonal antibody nivolumab.BMC bioinformatics · 2020Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundProgrammed cell death protein 1 (PD-1), a negative co-stimulatory molecule, plays crucial roles in immune escape. Blockade of the interaction between PD-1 and PD-L1 shows exciting clinical responses in a fraction of cancer patients and the success makes PD-1 as a valuable target in immune checkpoint therapy. For the rational design of PD-1 targeting modulators, the ligand binding mechanism of PD-1 should be well understood in prior.
methodsIn this study, we applied 50 ns molecular dynamics simulations to observe the structural properties of PD-1 molecule in both apo and ligand bound states, and we studied the structural features of PD-1 in human and mouse respectively.
resultsThe results showed that the apo hPD-1 was more flexible than that in PD-L1 bound state. We unexpectedly found that K135 was important for binding energy although it was not at the binding interface. Moreover, the residues which stabilized the interactions with PD-L1 were distinguished. Taking the dynamic features of these residues into account, we identified several residual sites where mutations may gain the function of ligand binding. The in vitro binding experiments revealed the mutants M70I, S87 W, A129L, A132L, and K135 M were better in ligand binding than the wild type PD-1.
conclusionsThe structural information from MD simulation combined with in silico mutagenesis provides guidance to design engineered PD-1 mutants to modulate the PD-1/PD-L1 pathway.
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