3DMolNavi: a web-based retrieval and navigation tool for flexible molecular shape comparison

Abstract

Background: Many molecules of interest are flexible and undergo significant shape deformation as part of their function, but most existing methods of molecular shape comparison treat them as rigid shapes, which may lead to incorrect measure of the shape similarity of flexible molecules. Currently, there still is a limited effort in retrieval and navigation for flexible molecular shape comparison, which would improve data retrieval by helping users locate the desirable molecule in a convenient way.

Results: To address this issue, we develop a web-based retrieval and navigation tool, named 3DMolNavi, for flexible molecular shape comparison. This tool is based on the histogram of Inner Distance Shape Signature (IDSS) for fast retrieving molecules that are similar to a query molecule, and uses dimensionality reduction to navigate the retrieved results in 2D and 3D spaces. We tested 3DMolNavi in the Database of Macromolecular Movements (MolMovDB) and CATH. Compared to other shape descriptors, it achieves good performance and retrieval results for different classes of flexible molecules.

Conclusions: The advantages of 3DMolNavi, over other existing softwares, are to integrate retrieval for flexible molecular shape comparison and enhance navigation for user's interaction. 3DMolNavi can be accessed via https://engineering.purdue.edu/PRECISE/3dmolnavi/index.html.

Figure 1

The illustration of flexible molecular shape comparison and similarity measure based on the IDSS histograms. Given a molecular shape, the whole process could be divided into three independent steps including sampling (red points) on the molecule, computing inner distances (green line segments) between all sample point pairs, and building the IDSS histogram. Consequently, our approach reduces the similarity measure among molecules to the comparison of IDSS histograms. An example is given for calculating the similarity measure between two different molecules (PDB codes: 1aon-A, 1irk-A), where the similarity score is equal to 0.6535.

Figure 2

Illustration of flexible molecular shape comparison and similarity measure between two conformations (PDB codes: 1j5n-A, 1lwm-A) of the same protein based on their IDSS histograms. The IDSS is not sensitive to shape deformation, and consequently, two conformations have a high similarity score equal to 0.8943.

Figure 3

The 3DMolNavi graphical interface.

Figure 4

Precision-recall curves compared to other descriptor methods for the MolMovDB database.