Deep Mapper: Efficient Visualization of Plausible Conformational Pathways

Acquiring plausible pathways on high-dimensional structural distributions is beneficial in several domains. For example, in the drug discovery field, a protein conformational pathway, i.e. a highly probable sequence of protein structural changes, is useful to analyze interactions between the protein and the ligands, helping to create new drugs. Recently, a state-of-the-art method in drug discovery was presented, which efficiently computes protein pathways using latent variables obtained from an isometric auto-encoding of the space of 3D density maps associated to protein conformations. However, our preliminary experiments show that there is room to significantly reduce the computing time. In this study, we use the Mapper algorithm, which is a Topological Data Analysis method, and present a novel variant to extract plausible conformational pathways from the isometric latent space with comparatively short running time. The extracted pathways are visualized as paths on the resulting Mapper graph. The methodological novelties are described as follows: firstly, the filter function of the Mapper algorithm is optimized so as to extract the pathways via minimization of an energy loss defined on the Mapper graph itself, while filter functions taken in the classical Mapper algorithm are fixed beforehand. The optimization is with respect to parameters of a deep neural network in the filter. Secondly, the clustering method, which defines the vertices and edges of the Mapper graph, of our algorithm is designed by incorporating domain prior knowledge to assist the extraction. In our numerical experiments, based on an isometric latent space built on the common 50S-ribosomal dataset, the resulting Mapper graph successfully includes all the well-recognized plausible pathways. Moreover, our running time is much shorter than the above state-of-the-art counterpart.