Behavioral science should start by assuming people are reasonable.

Should policymaking assume humans are irrational? Using empirical, theoretical, and philosophical arguments, we suggest a more useful frame is that human behavior is reasonable. Through identifying goals and systemic factors shaping behavior, we suggest that assuming people are reasonable enables behavioral science to be more effective in shaping public policy.

Using more than 801 296 small-molecule crystal structures to aid in protein structure refinement and analysis. Addendum.

An addendum to the Introduction of Cole et al. [(2017), Acta Cryst. D73, 234-239] is made to recognize the work of Bricogne, Smart and others in the development of methods to make use of Cambridge Structural Database data in protein structure solution.

The use of small-molecule structures to complement protein-ligand crystal structures in drug discovery.

Many ligand-discovery stories tell of the use of structures of protein-ligand complexes, but the contribution of structural chemistry is such a core part of finding and improving ligands that it is often overlooked. More than 800 000 crystal structures are available to the community through the Cambridge Structural Database (CSD). Individually, these structures can be of tremendous value and the collection of crystal structures is even more helpful.

Using more than 801 296 small-molecule crystal structures to aid in protein structure refinement and analysis.

The Cambridge Structural Database (CSD) is the worldwide resource for the dissemination of all published three-dimensional structures of small-molecule organic and metal-organic compounds. This paper briefly describes how this collection of crystal structures can be used en masse in the context of macromolecular crystallography. Examples highlight how the CSD and associated software aid protein-ligand complex validation, and show how the CSD could be further used in the generation of geometrical restraints for protein structure refinement.

Generation of crystal structures using known crystal structures as analogues.

This analysis attempts to answer the question of whether similar molecules crystallize in a similar manner. An analysis of structures in the Cambridge Structural Database shows that the answer is yes - sometimes they do, particularly for single-component structures. However, one does need to define what we mean by similar in both cases.

Report on the sixth blind test of organic crystal structure prediction methods.

The sixth blind test of organic crystal structure prediction (CSP) methods has been held, with five target systems: a small nearly rigid molecule, a polymorphic former drug candidate, a chloride salt hydrate, a co-crystal and a bulky flexible molecule. This blind test has seen substantial growth in the number of participants, with the broad range of prediction methods giving a unique insight into the state of the art in the field. Significant progress has been seen in treating flexible molecules, usage of hierarchical approaches to ranking structures, the application of density-functional approximations, and the establishment of new workflows and `best practices' for performing CSP calculations.

Capturing neon - the first experimental structure of neon trapped within a metal-organic environment.

Despite being the fifth most abundant element in the atmosphere, neon has never been observed in an organic or metal-organic environment. This study shows the adsorption of this highly unreactive element within such an environment and reveals the first crystallographic observation of an interaction between neon and a transition metal.

Hydrogen bonding at C=Se acceptors in selenoureas, selenoamides and selones.

In recent years there has been considerable interest in chalcogen and hydrogen bonding involving Se atoms, but a general understanding of their nature and behaviour has yet to emerge. In the present work, the hydrogen-bonding ability and nature of Se atoms in selenourea derivatives, selenoamides and selones has been explored using analysis of the Cambridge Structural Database and ab initio calculations. In the CSD there are 70 C=Se structures forming hydrogen bonds, all of them selenourea derivatives or selenoamides.

Outcome of the First wwPDB/CCDC/D3R Ligand Validation Workshop.

Crystallographic studies of ligands bound to biological macromolecules (proteins and nucleic acids) represent an important source of information concerning drug-target interactions, providing atomic level insights into the physical chemistry of complex formation between macromolecules and ligands. Of the more than 115,000 entries extant in the Protein Data Bank (PDB) archive, ∼75% include at least one non-polymeric ligand. Ligand geometrical and stereochemical quality, the suitability of ligand models for in silico drug discovery and design, and the goodness-of-fit of ligand models to electron-density maps vary widely across the archive.

The Cambridge Structural Database.

The Cambridge Structural Database (CSD) contains a complete record of all published organic and metal-organic small-molecule crystal structures. The database has been in operation for over 50 years and continues to be the primary means of sharing structural chemistry data and knowledge across disciplines. As well as structures that are made public to support scientific articles, it includes many structures published directly as CSD Communications.

Identifying Interactions that Determine Fragment Binding at Protein Hotspots.

Locating a ligand-binding site is an important first step in structure-guided drug discovery, but current methods do little to suggest which interactions within a pocket are the most important for binding. Here we illustrate a method that samples atomic hotspots with simple molecular probes to produce fragment hotspot maps. These maps specifically highlight fragment-binding sites and their corresponding pharmacophores.

Knowledge-Based Optimization of Molecular Geometries Using Crystal Structures.

This paper describes a novel way to use the structural information contained in the Cambridge Structural Database (CSD) to drive geometry optimization of organic molecules. We describe how CSD structural information is transformed into objective functions for gradient-based optimization to provide good quality geometries for a large variety of organic molecules. Performance is assessed by minimizing different sets of organic molecules reporting RMSD movements for bond lengths, valence angles, torsion angles, and heavy atom positions.

Interactive and Versatile Navigation of Structural Databases.

We present CSD-CrossMiner, a novel tool for pharmacophore-based searches in crystal structure databases. Intuitive pharmacophore queries describing, among others, protein-ligand interaction patterns, ligand scaffolds, or protein environments can be built and modified interactively. Matching crystal structures are overlaid onto the query and visualized as soon as they are available, enabling the researcher to quickly modify a hypothesis on the fly.

A review of methods for the calculation of solution free energies and the modelling of systems in solution.

Over the past decade, pharmaceutical companies have seen a decline in the number of drug candidates successfully passing through clinical trials, though billions are still spent on drug development. Poor aqueous solubility leads to low bio-availability, reducing pharmaceutical effectiveness. The human cost of inefficient drug candidate testing is of great medical concern, with fewer drugs making it to the production line, slowing the development of new treatments.

Data to knowledge: how to get meaning from your result.

Structural and functional studies require the development of sophisticated 'Big Data' technologies and software to increase the knowledge derived and ensure reproducibility of the data. This paper presents summaries of the Structural Biology Knowledge Base, the VIPERdb Virus Structure Database, evaluation of homology modeling by the Protein Model Portal, the ProSMART tool for conformation-independent structure comparison, the LabDB 'super' laboratory information management system and the Cambridge Structural Database. These techniques and technologies represent important tools for the transformation of crystallographic data into knowledge and information, in an effort to address the problem of non-reproducibility of experimental results.

A crystallographic perspective on sharing data and knowledge.

The crystallographic community is in many ways an exemplar of the benefits and practices of sharing data. Since the inception of the technique, virtually every published crystal structure has been made available to others. This has been achieved through the establishment of several specialist data centres, including the Cambridge Crystallographic Data Centre, which produces the Cambridge Structural Database.

Sixth blind test of organic crystal-structure prediction methods.

Over the past 15 years progress in predicting crystal structures of small organic molecules has been charted by a series of blind tests hosted by the Cambridge Crystallographic Data Centre. This letter announces a sixth blind test to take place between September 2014 and August 2015, giving details of the target systems and the revised procedure. We hope that as many methods as possible will be assessed and benchmarked in this new blind test.

The Cambridge Structural Database in retrospect and prospect.

The Cambridge Crystallographic Data Centre (CCDC) was established in 1965 to record numerical, chemical and bibliographic data relating to published organic and metal-organic crystal structures. The Cambridge Structural Database (CSD) now stores data for nearly 700,000 structures and is a comprehensive and fully retrospective historical archive of small-molecule crystallography. Nearly 40,000 new structures are added each year.

The hydrogen bond environments of 1H-tetrazole and tetrazolate rings: the structural basis for tetrazole-carboxylic acid bioisosterism.

Bioisosterism involving replacement of a carboxylic acid substituent by 1H-tetrazole, yielding deprotonated carboxylate and tetrazolate under physiological conditions, is a well-known synthetic strategy in medicinal chemistry. To improve our overall understanding of bioisosterism, we have used this example to study the geometrical and energetic aspects of the functional group replacement. Specifically, we use crystal structure informatics and high-level ab initio calculations to study the hydrogen bond (H-bond) energy landscapes of the protonated and deprotonated bioisosteric pairs.

The good, the bad and the twisted: a survey of ligand geometry in protein crystal structures.

The protein databank now contains the structures of over 11,000 ligands bound to proteins. These structures are invaluable in applied areas such as structure-based drug design, but are also the substrate for understanding the energetics of intermolecular interactions with proteins. Despite their obvious importance, the careful analysis of ligands bound to protein structures lags behind the analysis of the protein structures themselves.

Evaluating the usability of a single UK community acquired brain injury (ABI) rehabilitation service website: implications for research methodology and website design.

Information provision is an important resource for those living with acquired brain injury (ABI) and their families. Web-based health information services are now common additions to health service provision. Ideally, they should be easy to use and provide useful, relevant and accurate information.

Atomic interactions and profile of small molecules disrupting protein-protein interfaces: the TIMBAL database.

Growing evidence of the possibility of modulating protein-protein interactions with small molecules is opening the door to new approaches and concepts in drug discovery. In this paper, we describe the creation of TIMBAL, a hand-curated database holding an up to date collection of small molecules inhibiting multi-protein complexes. This database has been analysed and profiled in terms of molecular properties.