PD-1与单克隆抗体残基特异性结合机制的计算丙氨酸扫描研究

Molecular dynamics simulations were conducted on two PD-1/monoclonal antibody(pembrolizu-mab, nivolumab) complexes separately. The binding hotspots of the monoclonal antibody(mAb) and PD-1 were predicted by using efficient computational alanine scanning method. The comparation between the predicted hotspots and the important residues in PD-1/PD-L1 complex shows that pembrolizumab combines with PD-1 in a way similar to PD-L1, while nivolumab combines with PD-1 in a more different way by N-loop. _PD-1K131 is the only hotspot shared by the two PD-1/mAb complexes. It is also found that key residues of mAbs binding to _D-1K131 are similarly dominated by van der Waals(vdW) energy. Furthermore, hotspots on both the monoclonal antibodies are dominated by vdW energy, indicating a demand to improve the contributions of electrostatic energy. The present work provides important insights for the design of new mAbs targeting PD-1.