论文标题
生成目标蛋白结合的3D分子
Generating 3D Molecules for Target Protein Binding
论文作者
论文摘要
药物发现中的一个基本问题是设计与特定蛋白质结合的分子。为了使用机器学习方法解决这个问题,在这里,我们提出了一个新颖有效的框架,称为GraphBP,以生成3D分子,通过将特定类型和位置的原子放置在给定的结合位点上。特别是,在每个步骤中,我们首先采用3D图神经网络从中间的上下文信息中获得几何学感知和化学信息丰富的表示。这样的上下文包括前一步中放置的给定绑定位点和原子。其次,为了保留所需的均值属性,我们根据设计的辅助分类器选择局部参考原子,然后构建局部球形坐标系。最后,要放置一个新的原子,我们生成其原子类型和相对位置W.R.T.通过流模型构建的本地坐标系。我们还考虑依次生成感兴趣的变量,以捕获它们之间的基本依赖性。实验表明,我们的GraphBP有效地产生具有靶向蛋白结合位点的结合能力的3D分子。我们的实现可在https://github.com/divelab/graphbp上获得。
A fundamental problem in drug discovery is to design molecules that bind to specific proteins. To tackle this problem using machine learning methods, here we propose a novel and effective framework, known as GraphBP, to generate 3D molecules that bind to given proteins by placing atoms of specific types and locations to the given binding site one by one. In particular, at each step, we first employ a 3D graph neural network to obtain geometry-aware and chemically informative representations from the intermediate contextual information. Such context includes the given binding site and atoms placed in the previous steps. Second, to preserve the desirable equivariance property, we select a local reference atom according to the designed auxiliary classifiers and then construct a local spherical coordinate system. Finally, to place a new atom, we generate its atom type and relative location w.r.t. the constructed local coordinate system via a flow model. We also consider generating the variables of interest sequentially to capture the underlying dependencies among them. Experiments demonstrate that our GraphBP is effective to generate 3D molecules with binding ability to target protein binding sites. Our implementation is available at https://github.com/divelab/GraphBP.