iSyn: WebGL-Based Interactive De Novo Drug Design

Abstract

We present iSyn, a WebGL-based tool for interactivede novo drug design. It features an evolutionary algorithm that automatically designs novel ligands with drug-like properties and synthetic feasibility using click chemistry. Isyn interfaces with our popular and fast molecular docking engine idock, remarkably reducing the evaluation and ranking time of drug candidates. Furthermore, inspired by our user friendly and high-performance WebGL visualizer iview, our iSyn also implements a tailor-made interactive visualizer to aid novel drug design. We believe iSyn can supplement the efforts of medicinal chemists in drug discovery research. To illustrate the utility of iSyn in generating novelligands ex nihilo, we designed predicted inhibitors of two important drug targets, which are RNA editing ligase 1(REL1) from T. Brucei, the etiological agent of African sleeping sickness, and cyclin-dependent kinase 2 (CDK2), a positive regulator of eukaryotic cell cycle progression. Results show that iSyn managed to significantly enhance the predicted binding affinity of the best generated ligand by more than 3 orders of magnitude in potency. Isyn is written in C++, Python, HTML5 and JavaScript. It is free and open source, available athttp://istar.cse.cuhk.edu.hk/iSyn.tgz. It has been tested successfully on both Linux and Windows.