Modern structure-based design encompasses hundreds of methods, advanced algorithms and diverse biological targets. Cresset has a long-standing reputation for easy to use applications in the ligand-based design sphere. In deciding to bring Flare™, a new structure-based design application, to the market we created a challenge – can structure-based design be made simple?

A balance of usability and flexibility

Usability and flexibility are such fundamental features of well-designed software that they are often only noticed when they are absent. Usability reduces frustration, reduces training overhead, and makes it easier to access the full potential of the software. However, users also want the flexibility to tweak experiments, perform complex workflows and customise their applications to work the way they do. These key ‘unspoken’ features have been part of the design process in building Flare from the very start.

Focus on design

Critical to any analysis is the use of your conclusions to change the future. In structure-based design this means using information on how ligands bind to proteins to influence the design of the next ligand. In Flare we have put ligands at the heart of the application. They are stored in their own table and have a dedicated tab menu. The table layout enables physico-chemical property data to be stored alongside each ligand or calculated for every new design. It enables you to organize your compounds (sorting ligands based on their properties) or split ligands into different groups (roles) so that you can break down larger datasets into manageable chunks.

Designing new ligands is easy using the simple ‘Edit a copy’ feature. This brings up the molecular editor where the ligand can be improved in the protein active site and in reference to other ligands. The combination makes it easy to design in 3D, gaining all the productivity benefits that this brings. Sequential edits give an iterative process where each new design can be analysed and used as the basis for the next design.

Accessible methods

Analysis of existing or newly designed ligands requires complex methods. From docking to a detailed energetic prediction of binding, structure-based design methods are all complex. The challenge here is to present complex methods in an accessible way that enables expert users to modify key parameters but is not daunting to the regular user. In Flare a standardised layout is used for all calculation dialogues and provide default settings that work well in most cases. Experts have the choice to take the defaults or progress to the Advanced Options to change the parameters to meet their needs.

Great pictures

Creating great pictures is central to structure-based design. It seems like no J. Med. Chem. Article is complete without at least one protein-ligand picture. Creating pictures in Flare is easy with control over every aspect of the 3D display straight from the Home tab menu. Add to these the ability to control the clipping planes of surfaces independently of atoms and bonds and control over the picture resolution and you have all the elements you need to make stunning pictures. Whether for internal presentations, print articles or large posters, Flare delivers the quality of picture that you need.

Free evaluation of Flare

The feedback that we have received on the usability of Flare has been very positive. In the next release, you will see even more usability features such as storyboards, improved ligand selection and enhancements to the drag and drop features. We want Flare to be the best structure-based design application you use, so share your experience with us.

Request a free evaluation of Flare to see for yourself just how accessible structure-based design is for computational, medicinal and synthetic chemists.