Protein internal dynamics is essential for its function. Exploring the internal dynamics of protein molecules as well as its connection to protein structure and function is a central topic in biophysics. However, the ...Protein internal dynamics is essential for its function. Exploring the internal dynamics of protein molecules as well as its connection to protein structure and function is a central topic in biophysics. However, the atomic motions in protein molecules exhibit a great degree of complexities. These complexities arise from the complex chemical composition and superposition of different types of atomic motions on the similar time scales, and render it challenging to explicitly understand the microscopic mechanism governing protein motions, functions, and their connections. Here, we demonstrate that, by using neutron scattering, molecular dynamics simulation, and deuteration technique, one can address this challenge to a large extent.展开更多
Monoclonal antibodies are attractive therapeutic agents in a wide range of human disorders that bind specifically to their target through their complementary-determining regions(CDRs).Small proteins with structurally ...Monoclonal antibodies are attractive therapeutic agents in a wide range of human disorders that bind specifically to their target through their complementary-determining regions(CDRs).Small proteins with structurally preserved CDRs are promising antibodies mimetics.In this in silico study,we presented new antibody mimetics against the cancer marker epidermal growth factor receptor(EGFR)created by the CDRs grafting technique.Ten potential graft acceptor sites that efficiently immobilize the grafted CDR loops were selected from three small protein scaffolds using a computer.The three most involved CDR loops in antibody-receptor interactions extracted from panitumumab antibody against the EGFR domain III crystal structure were then grafted to the selected scaffolds through the loop randomization technique.The combination of three CDR loops and 10 grafting sites revealed that three of the 36 combinations showed specific binding to EGFR DIII by binding energy calculations.Thus,the present strategy and selected small protein scaffolds are promising tools in the design of new binders against EGFR with high binding energy.展开更多
基金financially supported by the National Natural Science Foundation of China (Nos. 11504231 and 31630002)the Innovation Program of Shanghai Municipal Education Commission
文摘Protein internal dynamics is essential for its function. Exploring the internal dynamics of protein molecules as well as its connection to protein structure and function is a central topic in biophysics. However, the atomic motions in protein molecules exhibit a great degree of complexities. These complexities arise from the complex chemical composition and superposition of different types of atomic motions on the similar time scales, and render it challenging to explicitly understand the microscopic mechanism governing protein motions, functions, and their connections. Here, we demonstrate that, by using neutron scattering, molecular dynamics simulation, and deuteration technique, one can address this challenge to a large extent.
文摘Monoclonal antibodies are attractive therapeutic agents in a wide range of human disorders that bind specifically to their target through their complementary-determining regions(CDRs).Small proteins with structurally preserved CDRs are promising antibodies mimetics.In this in silico study,we presented new antibody mimetics against the cancer marker epidermal growth factor receptor(EGFR)created by the CDRs grafting technique.Ten potential graft acceptor sites that efficiently immobilize the grafted CDR loops were selected from three small protein scaffolds using a computer.The three most involved CDR loops in antibody-receptor interactions extracted from panitumumab antibody against the EGFR domain III crystal structure were then grafted to the selected scaffolds through the loop randomization technique.The combination of three CDR loops and 10 grafting sites revealed that three of the 36 combinations showed specific binding to EGFR DIII by binding energy calculations.Thus,the present strategy and selected small protein scaffolds are promising tools in the design of new binders against EGFR with high binding energy.
