Redesigning an Antibody Fragment for Faster Association with Its Antigen

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• 作者：Jonathan S. Marvin and Henry B. Lowman
• 刊名：Biochemistry
• 出版年：2003
• 出版时间：June 17, 2003
• 年：2003
• 卷：42
• 期：23
• 页码：7077 - 7083
• 全文大小：259K
• 年卷期：v.42,no.23(June 17, 2003)
• ISSN：1520-4995

文摘

Traditional approaches for increasing the affinity of protein-protein complexes focus onconstructing highly complementary binding surfaces. Recent theoretical simulations and experimentalresults suggest that electrostatic steering forces can also be manipulated to increase association rates whileleaving dissociation rates unchanged, thus increasing affinity. Here we demonstrate that electrostaticattraction can be enhanced between an antibody fragment and its cognate antigen through application ofa few simple rules to identify potential on-rate amplification sites that lie at the periphery of the antigen-antibody interface.