Robert A. Nicholls

REFMAC5 for the refinement of macromolecular crystal structures

The general principles behind the macromolecular crystal structure refinement program REFMAC5 are described.

Tools for macromolecular model building and refinement into electron cryo-microscopy reconstructions.

A description is given of new tools to facilitate model building and refinement into electron cryo-microscopy reconstructions.

Low-resolution refinement tools in REFMAC5

Low-resolution refinement tools implemented in REFMAC5 are described, including the use of external structural restraints, helical restraints and regularized anisotropic map sharpening.

Conformation‐independent structural comparison of macromolecules with ProSMART

The Procrustes Structural Matching Alignment and Restraints Tool (ProSMART) has been developed to allow local comparative structural analyses independent of the global conformations and sequence homology of the compared macromolecules. This allows quick and intuitive visualization of the conservation of backbone and side-chain conformations, providing complementary information to existing methods.

Muts/Mutl Crystal Structure Reveals that the Muts Sliding Clamp Loads Mutl Onto DNA.

To avoid mutations in the genome, DNA replication is generally followed by DNA mismatch repair (MMR). MMR starts when a MutS homolog recognizes a mismatch and undergoes an ATP-dependent transformation to an elusive sliding clamp state. How this transient state promotes MutL homolog recruitment and activation of repair is unclear. Here we present a crystal structure of the MutS/MutL complex using a site-specifically crosslinked complex and examine how large conformational changes lead to activation of MutL. The structure captures MutS in the sliding clamp conformation, where tilting of the MutS subunits across each other pushes DNA into a new channel, and reorientation of the connector domain creates an interface for MutL with both MutS subunits. Our work explains how the sliding clamp promotes loading of MutL onto DNA, to activate downstream effectors. We thus elucidate a crucial mechanism that ensures that MMR is initiated only after detection of a DNA mismatch. DOI: http://dx.doi.org/10.7554/eLife.06744.001

AceDRG: a stereochemical description generator for ligands

The program AceDRG generates accurate stereochemical descriptions, and one or more conformations, of a given ligand. The program also analyses entries and extracts local environment-dependent atom types, bonds and angles from the Crystallography Open Database.

Diagnostic accuracy for major depression in multiple sclerosis using self-report questionnaires

Multiple sclerosis and major depressive disorder frequently co‐occur but depression often remains undiagnosed in this population. Self‐rated depression questionnaires are a good option where clinician‐based standardized diagnostics are not feasible. However, there is a paucity of data on diagnostic accuracy of self‐report measures for depression in multiple sclerosis (MS). Moreover, head‐to‐head comparisons of common questionnaires are largely lacking. This could be particularly relevant for high‐risk patients with depressive symptoms. Here, we compare the diagnostic accuracy of the Beck Depression Inventory (BDI) and 30‐item version of the Inventory of Depressive Symptomatology Self‐Rated (IDS‐SR30) for major depressive disorder (MSS) against diagnosis by a structured clinical interview.

CCP4i2: the new graphical user interface to the CCP4 program suite

CCP4i2 is a graphical user interface to the CCP4 (Collaborative Computational Project, Number 4) software suite and a Python language framework for software automation.

Validation and extraction of molecular-geometry information from small-molecule databases

The entries from a freely available small-molecule database, the Crystallography Open Database, have been validated and a reliable subset of molecules has been selected for the extraction of molecular-geometry information. The atom types and corresponding bond and angle classes derived from this database have been subjected to validation, the results of which are used by AceDRG in the derivation of new ligand descriptions.

Data to knowledge: how to get meaning from your result

This paper presents a variety of techniques and technologies aimed at the transformation of crystallographic data into information and knowledge.