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    • 8. 发明申请
    • Scoring Function Penalizing Compounds Which Desolvate Charged Protein Side Chains Structure
    • 评分功能处罚化合物,其中脱蛋白带电蛋白质侧链结构
    • US20120252687A1
    • 2012-10-04
    • US13079489
    • 2011-04-04
    • Richard A. FriesnerRobert Murphy
    • Richard A. FriesnerRobert Murphy
    • C40B30/04
    • G16C20/50G16B15/00
    • A method of scoring binding affinity of a proposed ligand molecule for a receptor molecule using a computer and computer data bases, which accounts for the increase in energy required where docking disrupts water molecules that are localized or localized. The method uses computer-stored data representing a predicted ligand-receptor structure (preferably one that is validated) as well as computer-stored data representing a library of compounds to be tested. Data representing members of the compound library is analyzed by computerized operations which determine whether the receptor in the predicted ligand-receptor structure includes a) determining whether the receptor in the predicted ligand-receptor structure includes solvating water molecule(s) whose desolvation into the surrounding environment requires substantial energy, b) determining whether a docking configuration for a member of the compound library with the receptor requires desolvation of one or more of the desolvating water molecule(s), and, if so, assigning a desolvation penalty to the member of the compound library.
    • 使用计算机和计算机数据库评估所提出的配体分子对受体分子的结合亲和力的方法,其考虑到对接破坏定位或定位的水分子所需的能量的增加。 该方法使用表示预测的配体 - 受体结构(优选经过验证的)的计算机存储的数据以及表示待测化合物文库的计算机存储的数据。 通过计算机操作来分析表示化合物文库的成员的数据,其确定预测的配体 - 受体结构中的受体是否包括a)确定预测的配体 - 受体结构中的受体是否包含溶解到周围的溶剂化水分子 环境需要大量的能量,b)确定化合物文库与受体的成员的对接构型是否需要脱溶剂中的一种或多种去溶质水分子,如果是,则将脱溶剂处罚分配给 复合库。
    • 9. 发明授权
    • Binding affinity scoring function including factor for environs of ring or bulky rigid group
    • 结合亲和力评分函数包括环或笨重刚性组的环境因子
    • US08160820B2
    • 2012-04-17
    • US12152067
    • 2008-05-12
    • Richard A. FriesnerRobert Murphy
    • Richard A. FriesnerRobert Murphy
    • G06F19/10
    • G06F19/706G06F19/16G06F19/707
    • Scoring functions can be markedly improved by taking into account the status environs of ligand rings (or indeed other bulky rigid ligand structures) on the ligand when the ligand is complexed with the receptor. In its most general form, the invention features, quantifying a particular component of binding affinity between a ligand and a receptor molecule. Specifically, the component in question takes into account the spatial relationship between ligand ring structure(s) (or bulky rigid ligand structures) and their ambient surroundings when the ligand is bound to the receptor molecule. The method steps may be used when quantifying a component that reflects these particular ligand features alone, or the steps may be part of a comprehensive method of quantifying binding affinity which includes numerous other factors that relate to binding affinity in addition to the component. For example, one may calculate an initial binding affinity and then adjust the initial binding affinity by a factor obtained at least in part based on the classification of the ring structure.
    • 当配体与受体复合时,通过考虑配体环(或实际上其它体积大的刚性配体结构)在配体上的状态环境,可以显着改善评分功能。 在其最通用形式中,本发明的特征在于定量配体和受体分子之间的结合亲和力的特定组分。 具体来说,当配体与受体分子结合时,所讨论的组分考虑了配体环结构(或体积大的刚性配体结构)及其周围环境之间的空间关系。 当量化单独反映这些特定配体特征的组分时,可以使用方法步骤,或者步骤可以是量化结合亲和力的全面方法的一部分,其包括与组分相关的结合亲和力相关的许多其它因子。 例如,可以计算初始结合亲和力,然后基于环结构的分类至少部分获得的因子来调整初始结合亲和力。