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    Methods and systems for analyzing and determining ligand-residue interaction
    6.
    发明申请
    Methods and systems for analyzing and determining ligand-residue interaction 失效
    用于分析和测定配体 - 残基相互作用的方法和系统

    公开(公告)号：US20050123995A1

    公开(公告)日：2005-06-09

    申请号：US10920234

    申请日：2004-08-18

    申请人： Stephan Brunner ,  David Mosenkis ,  Frank Hollinger ,  William Chiang

    发明人： Stephan Brunner ,  David Mosenkis ,  Frank Hollinger ,  William Chiang

    IPC分类号： C12Q20060101 ,  G01N33/48 ,  G01N33/50 ,  G01N33/53 ,  G01N33/569 ,  G06F17/00 ,  G06F17/30 ,  G06F19/00 ,  G06F19/16

    CPC分类号： G01N33/5695 ,  G06F19/16 ,  G06F19/701 ,  G06F19/706

    摘要： A method implemented in the form of a computer simulation code for evaluating the free energy of binding between polypeptide amino acid residues and one or more molecular fragment types is presented. The basis of the method is a novel weighted Metropolis Monte Carlo approach for sampling the grand canonical ensemble. By making use of the properties of the grand canonical ensemble, the affinity of fragments for binding in the vicinity of each protein residue can be efficiently computed. The binding volume associated to each fragment-residue pair is estimated on the basis of a simple proximity criteria, and a useful affinity mapping of the protein surface can be obtained in this way. The analysis of such data for various fragment types provides valuable information to help identify protein binding sites, as well as to identify key fragments used for building potential drug leads.

    摘要翻译： 提出了一种用于评估多肽氨基酸残基与一种或多种分子片段类型之间的结合自由能的计算机模拟代码形式的方法。 该方法的基础是一种新颖的加权大都会蒙特卡罗方法，用于抽样大规模集合。 通过利用大规模集合的性质，可以有效地计算片段在每个蛋白质残基附近的结合亲和力。 基于简单的接近标准估计与每个片段 - 残基对相关联的结合体积，并且可以以这种方式获得蛋白质表面的有用亲和力图谱。 对于各种片段类型的这种数据的分析提供了有价值的信息，以帮助鉴定蛋白质结合位点，以及鉴定用于构建潜在药物引线的关键片段。

    Method for fragment preparation
    8.
    发明申请
    Method for fragment preparation 审中-公开
    片段制备方法

    公开(公告)号：US20050222776A1

    公开(公告)日：2005-10-06

    申请号：US10813553

    申请日：2004-03-31

    申请人： Jennifer Ludington ,  Ted Fujimoto ,  Frank Hollinger

    发明人： Jennifer Ludington ,  Ted Fujimoto ,  Frank Hollinger

    IPC分类号： G01N33/48 ,  G01N33/50 ,  G01N33/68 ,  G06F19/00

    CPC分类号： G01N33/6803 ,  G16B15/00

    摘要： A method for characterizing a molecular fragment to collect data related to the fragment that allows its evaluation for drug discovery purposes. Starting with a two-dimensional model of the fragment, an initial three-dimensional model of the fragment is derived. Conformers of the fragment are identified. The conformers are then clustered, and a representative conformer is selected from each cluster. An ab initio or semi-empirical calculation and analysis is performed on one or more of the selected conformers. Each atom in the selected conformer is then assigned a type. The selected conformer is analyzed to determine if it is structurally symmetric. If so, the three-dimensional model of the fragment is adjusted to reflect the symmetry. The size of the fragment is calculated to allow geometric analysis of how the fragment physically fits with the protein and/or other fragments. The solvation energy of the fragment is calculated. The free energy curve for the fragment is calculated. Derivatization points for the fragment are then determined; a score is then assigned to each derivatization point, reflecting the ease or difficulty in bonding at the derivatization points. The fragment is then assigned a name and categorized. The fragment and its data derived in the above process can then be stored in a database.

    摘要翻译： 用于表征分子片段以收集与该片段相关的数据的方法，其允许其评估药物发现目的。 从片段的二维模型开始，导出片段的初始三维模型。 确定片段的构象。 然后将构象异构体聚集，并从每个聚类中选择代表性构象。 对一个或多个所选构象进行从头或半经验的计算和分析。 然后将所选构象异构体中的每个原子分配一个类型。 分析所选择的构象异构体以确定其是否在结构上对称。 如果是这样，则调整片段的三维模型以反映对称性。 计算片段的大小以允许对片段与蛋白质和/或其他片段物理匹配的几何分析。 计算片段的溶剂化能。 计算片段的自由能曲线。 然后确定片段的衍生点; 然后将分数分配给每个衍生化点，反映在衍生化点处的粘合的容易性或难度。 然后将该片段分配一个名称并进行分类。 然后将上述过程中导出的片段及其数据存储在数据库中。

    Methods of determining ligand residue binding affinity
    9.
    发明申请
    Methods of determining ligand residue binding affinity 审中-公开
    确定配体残基结合亲和力的方法

    公开(公告)号：US20050123993A1

    公开(公告)日：2005-06-09

    申请号：US10730267

    申请日：2003-12-09

    申请人： Stephan Brunner ,  David Mosenkis ,  Frank Hollinger ,  William Chiang

    发明人： Stephan Brunner ,  David Mosenkis ,  Frank Hollinger ,  William Chiang

    IPC分类号： G01N33/48 ,  G01N33/50 ,  G01N33/53 ,  G01N33/569 ,  G06F19/00

    CPC分类号： G01N33/5695 ,  G16B15/00

    摘要： Methods and systems for determining the affinity between polypeptide amino acid residues and one or more molecular fragments, and for using the affinity values to aid in drug design including a computer simulation which calculates the interaction energy between a polypeptide and at least one molecular fragment. An affinity value is then assigned to at least one fragment and residue pair if the fragment is in the vicinity of the residue. Affinity values are used to rank fragments, build ligands and determine binding sites.

    摘要翻译： 用于确定多肽氨基酸残基与一个或多个分子片段之间的亲和力的方法和系统，以及用于使用亲和力值来辅助药物设计，包括计算多肽与至少一个分子片段之间的相互作用能的计算机模拟。 如果片段在残基附近，则将亲和力值分配给至少一个片段和残基对。 亲和力值用于对片段进行排序，构建配体并确定结合位点。