Computationally targeted evolutionary design
    2.
    发明申请
    Computationally targeted evolutionary design 审中-公开
    计算目标进化设计

    公开(公告)号:US20050003389A1

    公开(公告)日:2005-01-06

    申请号:US10788254

    申请日:2004-02-25

    CPC分类号: G16B15/00 G16B20/00

    摘要: The invention relates to improved methods for directed evolution of polymers, including directed evolution of nucleic acids and proteins. Specifically, the methods of the invention include analytical methods for identifying “structurally tolerant” residues of a polymer. Mutations of these, structurally tolerant residues are less likely to adversely affect desirable properties of a polymer sequence. The invention further provides improved methods for directed evolution wherein the structurally tolerant residues of a polymer are selectively mutated. Computer systems for implementing analytical methods of the invention are also provided.

    摘要翻译: 本发明涉及聚合物定向进化的改进方法,包括核酸和蛋白质的定向进化。 具体地,本发明的方法包括用于鉴定聚合物的“结构上耐受性”残留物的分析方法。 这些结构上耐受性残基的突变不太可能不利地影响聚合物序列的期望性质。 本发明还提供了用于定向进化的改进方法,其中聚合物的结构耐受性残基被选择性突变。 还提供了用于实现本发明的分析方法的计算机系统。

    Proteins with integrin-like activity

    公开(公告)号:US06951927B2

    公开(公告)日:2005-10-04

    申请号:US09902481

    申请日:2001-07-09

    CPC分类号: C07K14/70546 A61K38/00

    摘要: The invention relates to novel proteins with novel integrin and I domain activity and nucleic acids encoding these proteins. The invention further relates to the use of the novel proteins in the treatment of integrin related disorders. TABLE 1 Computationally designed mutantsa WTido1qido1rido2rjlm2r BackboneEnergyb 1ido−1037 −1145−1138−1116 −678 1jlm−1059+82758 −840−1000−1086 PositionResidues 139I——V— 153M——A— 156FLW—— 157V——I— 160VI——— 199VIII— 215ILL—V 219V———I 223F———L 238VFFII 239VLLL— 240ILL—— 259ALL—— 269IL——— 271VF——— 287IVVV— 299VAII— 308IV——— aMutants are named according to the structure that was stabilized (ido or jlm), the solvation potential used (1 or 2) and the definition of core residues (q or r). bThe lowest energy rotamer configuration was calculated for each sequence in the lido structure, and cross-calculated in the ljlm structure, using both solvent potentials; all 50 core residues were used in order to make the q and r energies comparable. Results are shown for solvent potential 1 and were similar for potential 2. # A severe clash of the side-chain of F271 with the backbone caused the high energy of the 1q sequence in the 1jlm structure; no movement of the backbone is allowed by the design method.