期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：6
页码：2591-2595
DOI：10.1073/pnas.96.6.2591
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Biological diversity has evolved despite the essentially infinite complexity of protein sequence space. We present a hierarchical approach to the efficient searching of this space and quantify the evolutionary potential of our approach with Monte Carlo simulations. These simulations demonstrate that nonhomologous juxtaposition of encoded structure is the rate-limiting step in the production of new tertiary protein folds. Nonhomologous "swapping" of low-energy secondary structures increased the binding constant of a simulated protein by {approx}107 relative to base substitution alone. Applications of our approach include the generation of new protein folds and modeling the molecular evolution of disease.
