An integrated suite of modeling tools that empower scientists in structure- and property-based drug design

• Published in: Journal of computer-aided molecular design Vol. 29; no. 6; pp. 511 - 523
• Main Authors: Feng, Jianwen A., Aliagas, Ignacio, Bergeron, Philippe, Blaney, Jeff M., Bradley, Erin K., Koehler, Michael F. T., Lee, Man-Ling, Ortwine, Daniel F., Tsui, Vickie, Wu, Johnny, Gobbi, Alberto
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2015
• Subjects: Animal Anatomy; Chemistry; Chemistry and Materials Science; Computer Applications in Chemistry; Computer-Aided Design; Drug Design; Histology; Molecular Conformation; Molecular Docking Simulation; Morphology; Physical Chemistry; Quantitative Structure-Activity Relationship; Software; TYK2 Kinase - antagonists & inhibitors; TYK2 Kinase - chemistry; Property-based drug design; CDK8 kinase; Software integration; Small molecule conformational analysis; Structure-based drug design; Desktop modeling applications; TYK2 kinase; Molecular property calculations; De novo design
• ISSN: 0920-654X; 1573-4951
• DOI: 10.1007/s10822-015-9845-4

Structure- and property-based drug design is an integral part of modern drug discovery, enabling the design of compounds aimed at improving potency and selectivity. However, building molecules using desktop modeling tools can easily lead to poor designs that appear to form many favorable interactions with the protein’s active site. Although a proposed molecule looks good on screen and appears to fit into the protein site X-ray crystal structure or pharmacophore model, doing so might require a high-energy small molecule conformation, which would likely be inactive. To help scientists make better design decisions, we have built integrated, easy-to-use, interactive software tools to perform docking experiments, de novo design, shape and pharmacophore based database searches, small molecule conformational analysis and molecular property calculations. Using a combination of these tools helps scientists in assessing the likelihood that a designed molecule will be active and have desirable drug metabolism and pharmacokinetic properties. Small molecule discovery success requires project teams to rapidly design and synthesize potent molecules with good ADME properties. Empowering scientists to evaluate ideas quickly and make better design decisions with easy-to-access and easy-to-understand software on their desktop is now a key part of our discovery process.