Lattice enumeration for inverse molecular design using the signature descriptor.
We describe an inverse quantitative structure-activity relationship (QSAR) framework developed for the design of molecular structures with desired properties. This framework uses chemical fragments encoded with a molecular descriptor known as a signature. It solves a system of linear constrained Diophantine equations to reorganize the fragments into novel molecular structures. The method has been previously applied to problems in drug and materials design but has inherent computational limitations due to the necessity of solving the Diophantine constraints. We propose a new approach to overcome these limitations using the Fincke-Pohst algorithm for lattice enumeration. We benchmark the new approach against previous results on LFA-1/ICAM-1 inhibitory peptides, linear homopolymers, and hydrofluoroether foam blowing agents. Software implementing the new approach is available at www.cs.otago.ac.nz/homepages/smartin.
Department of Computer Science, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand. smartin@cs.otago.ac.nz
Shawn
S
Martin
D000465:Algorithms; D015195:Drug Design; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship