Studies of protein-ligand interactions are helpful to elucidating the mechanisms of ligands, providing clues for rational drug design. The currently developed steered molecular dy- namics (SMD) is a complementary appr...Studies of protein-ligand interactions are helpful to elucidating the mechanisms of ligands, providing clues for rational drug design. The currently developed steered molecular dy- namics (SMD) is a complementary approach to experimental techniques in investigating the biochemical processes occurring at microsecond or second time scale, thus SMD may provide dynamical and kinetic processes of ligand-receptor binding and unbinding, which cannot be ac- cessed by the experimental methods. In this article, the methodology of SMD is described, and the applications of SMD simulations for obtaining dynamic insights into protein-ligand interactions are illustrated through two of our own examples. One is associated with the simulations of bind- ing and unbinding processes between huperzine A and acetylcholinesterase, and the other is concerned with the unbinding process of α-APAfrom HIV-1 reverse transcriptase.展开更多
1 Introduction X-ray diffraction is the major powerful method to resolve the problems on biological macromolecules in detail, but the large single crystals needed for analysis are usually.difficult to obtain. In contr...1 Introduction X-ray diffraction is the major powerful method to resolve the problems on biological macromolecules in detail, but the large single crystals needed for analysis are usually.difficult to obtain. In contrast to forming three-dimensional(3D) crystals, many proteins can form two-dimensional (2D) crystals easily. There have been several approaches to making 2D crystals. Lipid layer crystallization is a novel 2D crystallization method developed by Kornberg group. Some water-soluble proteins have been crystallized successfully by this method, and it can be possibly used to crystallize some intrinsic membrane proteins. The formed 2D crystals are展开更多
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.20102007,29725203 and 20072042)the State Key Program of Basic Research of China(Grant No.2002CB512802)+1 种基金the 863 Hi-Tech Program of China(Grant Nos.2002AA233011,2002AA233061,2001AA235051 and 2001AA 235041)Foundation of Shanghai Ministry of Science and Technology,and the Key Program of New Drug Research and Development from the Chinese Academy of Sciences.
文摘Studies of protein-ligand interactions are helpful to elucidating the mechanisms of ligands, providing clues for rational drug design. The currently developed steered molecular dy- namics (SMD) is a complementary approach to experimental techniques in investigating the biochemical processes occurring at microsecond or second time scale, thus SMD may provide dynamical and kinetic processes of ligand-receptor binding and unbinding, which cannot be ac- cessed by the experimental methods. In this article, the methodology of SMD is described, and the applications of SMD simulations for obtaining dynamic insights into protein-ligand interactions are illustrated through two of our own examples. One is associated with the simulations of bind- ing and unbinding processes between huperzine A and acetylcholinesterase, and the other is concerned with the unbinding process of α-APAfrom HIV-1 reverse transcriptase.
基金Project supported by the National Natural Science Foundation of China.
文摘1 Introduction X-ray diffraction is the major powerful method to resolve the problems on biological macromolecules in detail, but the large single crystals needed for analysis are usually.difficult to obtain. In contrast to forming three-dimensional(3D) crystals, many proteins can form two-dimensional (2D) crystals easily. There have been several approaches to making 2D crystals. Lipid layer crystallization is a novel 2D crystallization method developed by Kornberg group. Some water-soluble proteins have been crystallized successfully by this method, and it can be possibly used to crystallize some intrinsic membrane proteins. The formed 2D crystals are
