论文类型：期刊论文
发表刊物：MOLECULES
收录刊物：Scopus、PubMed、SCIE
卷号：20
期号：10
页面范围：19236-19251
ISSN号：1420-3049
关键字：binding affinity; steered molecular dynamics; rupture force; protein-ligand unbinding; optimization
摘要：Binding affinity prediction of protein-ligand complexes has attracted widespread interest. In this study, a self-adaptive steered molecular dynamics (SMD) method is proposed to reveal the binding affinity of protein-ligand complexes. The SMD method is executed through adjusting pulling direction to find an optimum trajectory of ligand dissociation, which is realized by minimizing the stretching force automatically. The SMD method is then used to simulate the dissociations of 19 common protein-ligand complexes which are derived from two homology families, and the binding free energy values are gained through experimental techniques. Results show that the proposed SMD method follows a different dissociation pathway with lower a rupture force and energy barrier when compared with the conventional SMD method, and further analysis indicates the rupture forces of the complexes in the same protein family correlate well with their binding free energy, which reveals the possibility of using the proposed SMD method to identify the active ligand.