Poster Sessions

BIOINFO-13

Sunghwan Kim

S. Kim, E. Bolton, S.H. Bryant

Sphericity Index and Oblate-Prolate Index: 3D Molecular-shaped Descriptors for Fast Structure Similarity Search

The similarity principle, which states that "structurally similar molecules have similar biological and pharmacological properties", is a crucial concept in rational drug design, especially useful for finding a molecule similar to a known active drug molecule when the structure of the drug molecule is available. The 3-dimensional (3D) structural similarity between two molecules can be estimated with their shape-Tanimoto (ST) value, but the ST value computation is not fast enough to screen a huge molecular library that typically contains more than millions of compounds. In the present study, the shape quadrupole moments of a molecule were used to devise two 3D shape descriptors (the sphericity index and the oblate-prolate index) that allow a simple and fast shape comparison between molecules. These two descriptors were used to analyze the shapes of ~16 million drug-like molecules available in the PubChem Compound database, a public molecular library at NIH. In addition, the descriptors were employed to design a prescreening scheme to speed 3D shape similarity searches by avoiding time-consuming ST computation as much as possible.