A fragment library based on gaussian mixtures predicting favorable molecular interactions
A fragment library based on gaussian mixtures predicting favorable molecular interactions
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DOI：
10.1006/jmbi.2001.5023
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发表时间：
2001-10-12
影响因子：
5.6
通讯作者：
Johnson, MS
中科院分区：
文献类型：
--
作者：
Rantanen, VV;Denessiouk, KA;Johnson, MS
本文描述了一个蛋白质原子-配体片段相互作用文库。该文库基于沉积在蛋白质数据库（PDB）中的蛋白质-配体和蛋白质-蛋白质复合物的实验解决结构，并且能够表征给定适合蛋白质的配体结构的结合位点。一组30个配体片段类型被定义为包括三个或更多原子，以便明确定义配体原子与其受体蛋白相互作用的参考框架。收集了配体片段与24类蛋白质靶原子以及一个水氧原子之间的相互作用，并按类型进行了分离。通过对单个碎片-目标原子对的空间分布进行视觉检测，获得了相互作用体积的粗粒度约束。满足这些约束的数据作为迭代期望最大化算法的输入，该算法产生有限高斯混合模型参数的最大似然估计作为输出。统计模式识别的概念和由此产生的混合模型密度(i)用于预测小球藻病毒DNA连接酶与其配体的腺嘌呤环之间的详细相互作用，（ii）用于评估PDB中发现的蛋白质-配体相互作用的训练集和验证集的预测“误差”。这些分析表明，这种方法可以成功地缩小相互作用的蛋白质原子类型及其相对于配体片段的位置的可能性。(C) 2001学术出版社。
Here, a protein atom-ligand fragment interaction library is described. The library is based on experimentally solved structures of protein-ligand and protein-protein complexes deposited in the Protein Data Bank (PDB) and it is able to characterize binding sites given a ligand structure suitable for a protein. A set of 30 ligand fragment types were defined to include three or more atoms in order to unambiguously define a frame of referencefor interactions of ligand atoms with their receptor proteins. Interactions between ligand fragments and 24 classes of protein target atoms plus a water oxygen atom were collected and segregated according to type. The spatial distributions of individual fragment - target atom pairs were visually inspected in order to obtain rough-grained constraints on the interaction volumes. Data fulfilling these constraints were given as input to an iterative expectation-maximization algorithm that produces as output maximum likelihood estimates of the parameters of the finite Gaussian mixture models. Concepts of statistical pattern recognition and the resulting mixture model densities are used (i) to predict the detailed interactions between Chlorella virus DNA ligase and the adenine ring of its ligand and (ii) to evaluate the "error" in prediction for both the training and validation sets of protein-ligand interaction found in the PDB. These analyses demonstrate that this approach can successfully narrow down the possibilities for both the interacting protein atom type and its location relative to a ligand fragment. (C) 2001 Academic Press.