Protein conformational transitions coupling with ligand interactions: Simulations from molecules to medicine

The functions and activities of proteins are closely related to their structures and dynamics, and their interactions with ligands. Knowledge of the mechanistic events of proteins’ conformational transitions and interactions with ligands is crucially important to understand the functions and biological activities of proteins and thus to the design of novel inhibitors of the targeted receptor. In this review article, taking two important systems as examples, i.e., human immunodeficiency virus type 1 protease (HIV-1 PR) and adenylate kinase (AdK), and focusing on the molecular dynamics simulations of the conformational transitions of protein and the protein-ligand association/dissociation, we explain how the conformational transitions of proteins influence the interactions with their ligands, and how the ligands impact the function and dynamics of proteins. These results of structural dynamics of HIV-1 PR and AdK and their interactions with ligands can help to understand the principle of conformational transitions of proteins, or the interactions of ligands to their biological targets, and thus provide meaningful message in chemistry and biology of drug design and discovery. •In this review article, taking two important systems as examples, i.e., the human immunodeficiency virus type 1 protease (HIV-1 PR) and adenylate kinase (AdK), and focusing on the molecular dynamics simulations of the conformational transitions of protein and the protein-ligand association/dissociation, we explain how the conformational transitions of proteins influence the interactions with their ligands, and how the ligands impact the function and dynamics of proteins.•These results of structural dynamics of HIV-1 PR and AdK and their interactions with ligands can help to understand the principle of conformational transitions of proteins, and the interactions of ligands to their biological targets, and thus provide meaningful Emessage in chemistry and biology of drug design and discovery.