文章基本信息

标题：Modeling evolutionary landscapes: Mutational stability, topology, and superfunnels in sequence space
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作者：Erich Bornberg-Bauer ; Hue Sun Chan
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：19
页码：10689-10694
DOI：10.1073/pnas.96.19.10689
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Random mutations under neutral or near-neutral conditions are studied by considering plausible evolutionary trajectories on "neutral nets"--i.e., collections of sequences (genotypes) interconnected via single-point mutations encoding for the same ground-state structure (phenotype). We use simple exact lattice models for the mapping between sequence and conformational spaces. Densities of states based on model intrachain interactions are determined by exhaustive conformational enumeration. We compare results from two very different interaction schemes to ascertain robustness of the conclusions. In both models, sequences in a majority of neutral nets center around a single "prototype sequence" of maximum mutational stability, tolerating the largest number of neutral mutations. General analytical considerations show that these topologies by themselves lead to higher steady-state evolutionary populations at prototype sequences. On average, native thermodynamic stability increases toward a maximum at the prototype sequence, resulting in funnel-like arrangements of native stabilities in sequence space. These observations offer a unified perspective on sequence design, native stability, and mutational stability of proteins. These principles are generalizable from native stability to any measure of fitness provided that its variation with respect to mutations is essentially smooth.
关键词：fitness landscapes ; neutral mutations ; folding funnels ; thermodynamic stability ; lattice protein models