The freedom space - a new set of commercially available molecules for hit discovery.

The advent of high-performance virtual screening techniques nowadays allows drug designers to explore ultra-large sets of candidate compounds in search of molecules predicted to have desired properties. However, the success of such an endeavor heavily relies on the pertinence (drug-likeness and, foremost, chemical feasibility) of these candidates, or otherwise, virtual screening will return valueless "hits", by the garbage in/garbage out principle. The huge popularity of the judiciously enumerated Enamine REAL Space is clear proof of the strength of this Big Data trend in drug discovery. Here we describe a new dataset of make-on-demand compounds called the Freedom space. It follows the principles of Enamine REAL Space and contains highly feasible molecules (synthesis success rate over 75 percent). However, the scaffold and chemography analysis revealed significant differences to both the REAL and biologically annotated compounds from the ChEMBL database. The Freedom Space is a significant extension of the REAL Space and can be utilized for a more comprehensive exploration of the synthetically feasible chemical space in hit finding and hit-to-lead campaigns.

Let the river erode! Enabling lateral migration increases geomorphic unit diversity.

River restoration practice frequently employs conservative designs that create and maintain prescribed, static morphology. Such approaches ignore an emerging understanding of resilient river systems that typically adjust their morphology in response to hydrologic, vegetative and sediment supply changes. As such, using increased dynamism as a restoration design objective will arguably yield more diverse and productive habitats, better managed expectations, and more self-sustaining outcomes. Here, we answer the following question: does restoring lateral migration in a channelised river that was once a wandering gravel-bed river, result in more diverse in-channel geomorphology? We acquired pre- and post-restoration topographic surveys on a segment of the Allt Lorgy, Scotland to quantify morphodynamics and systematically map geomorphic units, using Geomorphic Unit Tool (GUT) software. GUT implements topographic definitions to discriminate between a taxonomy of fluvial landforms that have been developed from an extension of the River Styles framework, using 3-tiered hierarchy: (1) differentiation based on stage or elevation relative to channel; (2) classification of form based on shape (mound, bowl, trough, saddle, plane, wall); and (3) mapping geomorphic units based on attributes (e.g., position and orientation). Results showed restoration increased geomorphic unit diversity, with the Shannon Diversity Index increasing from 1.40 pre-restoration (2012) to 2.04 (2014) and 2.05 (2016) after restoration. Channel widening, due to bank erosion, caused aerial coverage of in-channel geomorphic units to increase 23% after restoration and 6% further in the two-years following restoration. Once bank protection was removed, allowing bank erosion yieled a local supply of sediment to enable the formation and maintenance of lateral and point bars, riffles and diagonal bar complexes, and instream wood created structurally-forced pools and riffles. The methodology used systematically quantifies how geomorphic unit diversity increases when a river is given back its freedom space. The framework allows for testing restoration design hypotheses in post-project appraisal.