Exploration of Chemical Space by Molecular Morphing

Abstract

Many areas of chemical biology, such as drug discovery, rely heavily on chemical libraries offering compounds usable in the industrial processes. However, the "universe" containing all possible compounds, the so-called chemical space, is vast, and therefore, the libraries store only its representative parts. Thus, to explore the whole chemical space and to identify all its promising parts containing e.g., drug-like molecules computational methods have to be developed and employed. In this paper, we propose a method for traveling in the chemical space called Molpher. Given two molecules, Molpher is intended to find a sequence of related compounds, called path in the chemical space, leading from the starting molecule to the target one. The path is generated by iterative application of the so-called morphing operators corresponding to simple chemical operations such as adding or removing an atom or a bond. The molecules on the resulting path represent a focused library that can be used as a starting point for other experiments. We also propose a testbed for examining qualities of algorithms such as Molpher. The testbed is used to describe Molpher's qualities in terms of ability of finding a path in the space in the given time.