The design of high affinity human PD-1 mutants by using molecular dynamics simulations (MD).

ABSTRACT:

Background

Programmed 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.

Methods

In 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.

Results

The results showed that the apo hPD-1 was more flexible than that in PD-L1 bound

SUBMITTER: Du J 

PROVIDER: S-EPMC5992718 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature