折叠(DSP实现)
蛋白质折叠
球状蛋白
生物系统
计算生物学
蛋白质工程
蛋白质设计
结晶学
生物
蛋白质结构
生物物理学
计算机科学
化学
工程类
生物化学
酶
电气工程
作者
Mohammad ElGamacy,M.P. Coles,Andrei N. Lupas
标识
DOI:10.1016/j.jsb.2018.10.010
摘要
Computational design with supersecondary structures as building blocks has proven effective in the construction of new proteins with controlled geometries. So far, this approach has primarily exploited amplification, effectively harnessing the internal folding propensity of self-compatible fragments to achieve sufficient enthalpy for folding. Here we exploit an interface-driven strategy to depart from the repeat design realm, constructing an asymmetric, globular domain from heterologous supersecondary structures. We report the successful design of a dRP lyase domain fold, which agrees with the experimental NMR structure at atomic accuracy (backbone RMSD of 0.94 Å). Our results show that the residual folding information within conserved fragments, combined with efficient interface-directed sampling, can effectively yield globular proteins with novel sequences and biophysical properties.
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