Collaborative Computational Project Research Articles

Neutron crystallographic refinement with REFMAC5 from the CCP4 suite.

Hydrogen (H) atoms are abundant in macromolecules and often play critical roles in enzyme catalysis, ligand-recognition processes and protein-protein interactions. However, their direct visualization by diffraction techniques is challenging. Macromolecular X-ray crystallography affords the localization of only the most ordered H atoms at (sub-)atomic resolution (around 1.2 Å or higher). However, many H atoms of biochemical significance remain undetectable by this method. In contrast, neutron diffraction methods enable the visualization of most H atoms, typically in the form of deuterium (2H) atoms, at much more common resolution values (better than 2.5 Å). Thus, neutron crystallography, although technically demanding, is often the method of choice when direct information on protonation states is sought. REFMAC5 from the Collaborative Computational Project No. 4 (CCP4) is a program for the refinement of macromolecular models against X-ray crystallographic and cryo-EM data. This contribution describes its extension to include the refinement of structural models obtained from neutron crystallographic data. Stereochemical restraints with accurate bond distances between H atoms and their parent atom nuclei are now part of the CCP4 Monomer Library, the source of prior chemical information used in the refinement. One new feature for neutron data analysis in REFMAC5 is refinement of the protium/deuterium (1H/2H) fraction. This parameter describes the relative 1H/2H contribution to neutron scattering for hydrogenisotopes. The newly developed REFMAC5 algorithms were tested by performing the (re-)refinement of several entries available in the PDB and of one novel structure (FutA) using either (i) neutron data only or (ii) neutron data supplemented by external restraints to a reference X-ray crystallographic structure. Re-refinement with REFMAC5 afforded models characterized by R-factor values that are consistent with, and in some cases better than, the originally deposited values. The use of external reference structure restraints during refinement has been observed to be a valuable strategy, especially for structures at medium-low resolution.

The CCP4 suite: integrative software for macromolecular crystallography.

The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite instructure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.

Continuous development in macromolecular crystallography with CCP4.

The evolution of the Collaborative Computational Project No. 4 (CCP4) has been described in a new article by Agirre et al. [(2023). Acta Cryst. D79, 449-461] that should provide the definitive reference for the CCP4 suite of programs.

Simulating focused wave impacts on point absorber wave energy converters

This study contributes to the Collaborative Computational Project in Wave–Structure Interaction blind test series 2 by numerically investigating the dynamic response of two simplified point absorber wave energy converters (WECs – a hemispherical-bottom cylinder and a cylinder with moon-pool) under the action of focused waves of varying steepness. The open source toolbox OpenFOAM along with its new overset grid functionality is applied and evaluated for the complex flow problem involving both large free surface deformations and large-amplitude motions of floating objects. The quality of the numerically generated focused wave groups is first examined and validated against the experimental data. The effects of both wave steepness and the moon-pool on the dynamic responses and mooring loads of the simplified WECs are then analysed.

Modelling of focused wave interaction with wave energy converter models using qaleFOAM 

This paper presents a numerical investigation on the interaction between focused waves and wave energy converter (WEC) models using a hybrid solver, qaleFOAM, which couples a two-phase incompressible Navier–Stokes (NS) solver OpenFOAM/InterDyMFoam with the quasi Lagrangian–Eulerian finite element method (QALE-FEM) based on the fully non-linear potential theory (FNPT) using the domain-decomposition approach. In the qaleFOAM, the NS solver deals with a small region near the structures (NS domain), where the viscous effect may be significant; the QALE-FEM covers the remaining computational domain (FNPT domain); an overlap (transitional) zone is applied between two domains. The WEC models, mooring system and the wave conditions are given by the Collaborative Computational Project in Wave–Structure Interaction (CCP-WSI) Blind Test Series 2. In the numerical simulation, the incident wave is generated in the FNPT domain using a self-correction wavemaker and propagates into the NS domain through the coupling boundaries and attached transitional zones. An improved passive wave absorber is imposed at the outlet of the NS domain for wave absorption. The practical performance of the qaleFOAM is demonstrated by comparing its prediction with the experimental data, including the wave elevation, motion responses (surge, heave and pitch) and mooring load.

Wave–structure interaction of wave energy converters: a sensitivity analysis

Measurement uncertainties are inevitable during physical wave tank tests. Therefore, when validating a numerical wave tank against experiments, knowledge of the uncertainties in the physical experiments, and the sensitivity of the body dynamics to such uncertainties, is crucial. Specifically, the inertial properties, as well as the location of the centre of mass (CoM), which are challenging to measure accurately, can have a significant influence on the system dynamics. On the basis of test cases of the Collaborative Computational Project in Wave Structure Interaction Blind Test Series 2, this paper presents a sensitivity analysis of the agreement between experimental and numerical data sets to the quality of the incident, focused wave, as well as the inertial properties and the location of the CoM. A significant influence on the modelled system dynamics can be observed when changing the system parameters, resulting in a variation of the observed error of up to 80 percentage points for pitch motion.

Focused wave interactions with floating structures: a blind comparative study

The paper presents results from the Collaborative Computational Project in Wave Structure Interaction (CCP-WSI) Blind Test Series 2. Without prior access to the physical data, participants, with numerical methods ranging from low-fidelity linear models to fully non-linear Navier–Stokes (NS) solvers, simulate the interaction between focused wave events and two separate, taut-moored, floating structures: a hemispherical-bottomed cylinder and a cylinder with a moonpool. The ‘blind’ numerical predictions for heave, surge, pitch and mooring load, are compared against physical measurements. Dynamic time warping is used to quantify the predictive capability of participating methods. In general, NS solvers and hybrid methods give more accurate predictions; however, heave amplitude is predicted reasonably well by all methods; and a WEC-Sim implementation, with CFD-informed viscous terms, demonstrates comparable predictive capability to even the stronger NS solvers. Large variations in the solutions are observed (even among similar methods), highlighting a need for standardisation in the numerical modelling of WSI problems.

Blind test comparison of wave–structure interactions: a non-linear Froude–Krylov modelling approach

One of the essential stepping stones for reaching economic viability and industrial feasibility of the wave energy conversion sector is the effectiveness of the device design, which is dependent, among others, on the accuracy of mathematical models used for development. Despite being more than 45 years old, modelling is not mature yet and there is still a clear lack of standardisation of modelling techniques, and a need for increasing confidence in hydrodynamic models. The objective of the Collaborative Computational Project in Wave Structure Interaction is to critically compare and evaluate various different modelling techniques, under the same shared experimental conditions, and using clearly pre-defined metrics. This paper details a contribution implementing, in a computationally efficient way, non-linear Froude–Krylov forces and non-linear kinematics, with the goal to define a medium–high fidelity model, able to compute at a small fraction of the computational time typically required by fully non-linear models. The case study considers survivability-like wave conditions, represented by three steep focused waves, particularly challenging to be modelled using potential theory-based mathematical models. Despite a poor representation in pitch/surge, a good agreement with experimental heave response and mooring load is found, at small computation time, close to real-time computation.

Phase Distribution, Composition, and Disorder in Y2(Hf,Sn)2O7 Ceramics: Insights from Solid-State NMR Spectroscopy and First-Principles Calculations

The authors would like to thank the ERC (EU FP7 Consolidator Grant 614290 “‘EXONMR’”), and EPSRC for support for SS and ASG (EP/L005581/1). SEA would like to thank the Royal Society and Wolfson Foundation for a merit award. We acknowledge support from the Collaborative Computational Project on NMR Crystallography CCP-NC funded by EPSRC (EP/M022501/1).

Quantics: A general purpose package for Quantum molecular dynamics simulations

Quantics is a general purpose program package to simulate the time-evolution of a molecular system by solving the time-dependent Schrödinger equation. The main code is based on the multi-configurational time-dependent Hartree (MCTDH) algorithm in various variants, including the powerful multilayer-MCTDH algorithm that has been used to propagate a wavefunction for up to 1000 degrees of freedom. MCTDH uses a contraction of traditional discrete basis set representations of the Hamiltonian and wavefunction, and Quantics includes a range of variable representation (DVR) grid basis sets and collocation methods. Input is via ascii text files and for molecules with analytical potential functions no programming is required. A library of potential functions is included to treat more complicated cases, and more functions can be added as required by the user. The code also includes the variational multi-configurational Gaussian (vMCG) method that is based on a Gaussian wavepacket expansion of the wavefunction. vMCG can be run in a “direct” manner (DD-vMCG), calculating the potential energy surfaces on-the-fly using a number of quantum chemistry programs. In addition to wavepacket propagation, Quantics can solve the time-independent Schrödinger equation for small systems and can solve the Liouville–von-Neumann equation to propagate density matrices. The Package includes auxiliary programs to help set up calculations and analyse the output. Quantics is a community code of the UK Collaborative Computational Project for Quantum Dynamics (CCPQ) and the European E-CAM project, an e-infrastructure for software development run by the Centre Européen de Calcul Atomique et Moléculaire (CECAM). Through this it has become a framework for general dynamics codes, for example enabling an external surface hopping code to use the Quantics input and operator interfaces. Program summaryProgram Title: QuanticsProgram Files doi:http://dx.doi.org/10.17632/x9dcpc2r5c.1Licensing provisions: LGPLv3Programming language: Fortran90. Some Fortran77, Fortran2003, C and python.Nature of problem: Solving the time-dependent Schrödinger equation for a set of nuclei allows a range of physical processes to be studied including all quantum effects. This allows an experimental signal to be given a molecular interpretation. Typical applications are scattering cross-sections or time-resolved spectra, but also rate constants and other transport properties are possible. The exact problem to be solved is defined by the Hamiltonian, which must be provided by the user, and the initial wavepacket, again defined by the user. The final analysis of the evolving wavepacket then provides the experimental signal or molecular property.Solution method: A range of methods are possible for solving the time-evolution of a wavepacket (see main text). These can be broadly described as basis-set methods, in which the wavepacket and Hamiltonian are expanded in a set of functions. Various functions are possible, including grid-based sets (DVRs and collocation), and Gaussian wavepackets. The wavepacket can then be propagated using a variety of algorithms depending on the representation chosen. These include the full numerically-exact solution, various versions of the multi-configurational time-dependent Hartree method and approximate methods such as trajectory surface hopping. Full details are given in the documentation provided with the package and in a book and a number of review articles [1,2,3].Additional comments including restrictions and unusual features: The code has been tested on a number of linux distributions and compilers. It works best with a bash environment and a gnu gcc / gfortran compiler greater than version 4.8. The code is parallelised in parts using either OpenMP or MPI. There is a suite of test calculations to test an installation.

CCP-EM: the Collaborative Computational Project for Electron Cryo-Microscopy

CCP-EM: the Collaborative Computational Project for Electron Cryo-Microscopy

A Blind Comparative Study of Focused Wave Interactions with a Fixed FPSO-like Structure (CCP-WSI Blind Test Series 1)

Results from Blind Test Series 1, part of the Collaborative Computational Project in Wave Structure Interaction (CCP-WSI), are presented. Participants, with a range of numerical methods, simulate blindly the interaction between a fixed structure and focused waves ranging in steepness and direction. Numerical results are compared against corresponding physical data. The predictive capability of each method is assessed based on pressure and runup measurements. In general, all methods perform well in the cases considered; however, there is notable variation in the results (even between similar methods). Recommendations are made for appropriate considerations and analysis in future comparative studies.

A Picture of Disorder in Hydrous Wadsleyite-Under the Combined Microscope of Solid-State NMR Spectroscopy and Ab Initio Random Structure Searching.

The Earth’s transition zone, at depths of 410–660 km, while being composed of nominally anhydrous magnesium silicate minerals, may be subject to significant hydration. Little is known about the mechanism of hydration, despite the vital role this plays in the physical and chemical properties of the mantle, leading to a need for improved structural characterization. Here we present an ab initio random structure searching (AIRSS) investigation of semihydrous (1.65 wt % H2O) and fully hydrous (3.3 wt % H2O) wadsleyite. Following the AIRSS process, k-means clustering was used to select sets of structures with duplicates removed, which were then subjected to further geometry optimization with tighter constraints prior to NMR calculations. Semihydrous models identify a ground-state structure (Mg3 vacancies, O1–H hydroxyls) that aligns with a number of previous experimental observations. However, predicted NMR parameters fail to reproduce low-intensity signals observed in solid-state NMR spectra. In contrast, the fully hydrous models produced by AIRSS, which enable both isolated and clustered defects, are able to explain observed NMR signals via just four low-enthalpy structures: (i) a ground state, with isolated Mg3 vacancies and O1–H hydroxyls; (ii/iii) edge-sharing Mg3 vacancies with O1–H and O3–H species; and (iv) edge-sharing Mg1 and Mg3 vacancies with O1–H, O3–H, and O4–H hydroxyls. Thus, the combination of advanced structure searching approaches and solid-state NMR spectroscopy is able to provide new and detailed insight into the structure of this important mantle mineral.

DL_MESO_DPD: development and use of mesoscale modelling software

ABSTRACT DL_MESO is a highly-scalable general purpose software package for mesoscale modelling. Created and developed at Daresbury Laboratory for the UK Collaborative Computational Project CCP5, it was intended to be a companion package to the flagship molecular dynamics code DL_POLY. One of DL_MESO component codes, DL_MESO_DPD, is based on dissipative particle dynamics, a mesoscale modelling technique with many similarities to classical molecular dynamics. While this code and DL_POLY were created with different applications in mind, they share a significant amount of functionality and development history. This article gives an overview on how DL_MESO_DPD has been developed, including its shared history with DL_POLY and information on its current performance, and a selection of applications for which the code has been used.

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

The CCP4 (Collaborative Computational Project, Number 4) software suite for macromolecular structure determination by X-ray crystallography groups brings together many programs and libraries that, by means of well established conventions, interoperate effectively without adhering to strict design guidelines. Because of this inherent flexibility, users are often presented with diverse, even divergent, choices for solving every type of problem. Recently, CCP4 introduced CCP4i2, a modern graphical interface designed to help structural biologists to navigate the process of structure determination, with an emphasis on pipelining and the streamlined presentation of results. In addition, CCP4i2 provides a framework for writing structure-solution scripts that can be built up incrementally to create increasingly automatic procedures.

Forty years of collaborative computational crystallography.

A brief overview is provided of the history of collaborative computational crystallography, with an emphasis on the Collaborative Computational Project No. 4. The key steps in its development are outlined, with consideration also given to the underlying reasons which contributed, and ultimately led to, the unprecedented success of this venture.

Recent developments in the CCP-EM software suite.

As part of its remit to provide computational support to the cryo-EM community, the Collaborative Computational Project for Electron cryo-Microscopy (CCP-EM) has produced a software framework which enables easy access to a range of programs and utilities. The resulting software suite incorporates contributions from different collaborators by encapsulating them in Python task wrappers, which are then made accessible via a user-friendly graphical user interface as well as a command-line interface suitable for scripting. The framework includes tools for project and data management. An overview of the design of the framework is given, together with a survey of the functionality at different levels. The current CCP-EM suite has particular strength in the building and refinement of atomic models into cryo-EM reconstructions, which is described in detail.

Software for Distributed Computation on Medical Databases: A Demonstration Project

Bringing together the information latent in distributed medical databases promises to personalize medical care by enabling reliable, stable modeling of outcomes with rich feature sets (including patient characteristics and treatments received). However, there are barriers to aggregation of medical data, due to lack of standardization of ontologies, privacy concerns, proprietary attitudes toward data, and a reluctance to give up control over end use. Aggregation of data is not always necessary for model fitting. In models based on maximizing a likelihood, the computations can be distributed, with aggregation limited to the intermediate results of calculations on local data, rather than raw data. Distributed fitting is also possible for singular value decomposition. There has been work on the technical aspects of shared computation for particular applications, but little has been published on the software needed to support the social networking aspect of shared computing, to reduce the barriers to collaboration. We describe a set of software tools that allow the rapid assembly of a collaborative computational project, based on the flexible and extensible R statistical software and other open source packages, that can work across a heterogeneous collection of database environments, with full transparency to allow local officials concerned with privacy protections to validate the safety of the method. We describe the principles, architecture, and successful test results for the site-stratified Cox model and rank-k singular value decomposition.

Atomistic modelling of scattering data in the Collaborative Computational Project for Small Angle Scattering (CCP-SAS).

The capabilities of current computer simulations provide a unique opportunity to model small-angle scattering (SAS) data at the atomistic level, and to include other structural constraints ranging from molecular and atomistic energetics to crystallography, electron microscopy and NMR. This extends the capabilities of solution scattering and provides deeper insights into the physics and chemistry of the systems studied. Realizing this potential, however, requires integrating the experimental data with a new generation of modelling software. To achieve this, the CCP-SAS collaboration (http://www.ccpsas.org/) is developing open-source, high-throughput and user-friendly software for the atomistic and coarse-grained molecular modelling of scattering data. Robust state-of-the-art molecular simulation engines and molecular dynamics and Monte Carlo force fields provide constraints to the solution structure inferred from the small-angle scattering data, which incorporates the known physical chemistry of the system. The implementation of this software suite involves a tiered approach in which GenApp provides the deployment infrastructure for running applications on both standard and high-performance computing hardware, and SASSIE provides a workflow framework into which modules can be plugged to prepare structures, carry out simulations, calculate theoretical scattering data and compare results with experimental data. GenApp produces the accessible web-based front end termed SASSIE-web, and GenApp and SASSIE also make community SAS codes available. Applications are illustrated by case studies: (i) inter-domain flexibility in two- to six-domain proteins as exemplified by HIV-1 Gag, MASP and ubiquitin; (ii) the hinge conformation in human IgG2 and IgA1 antibodies; (iii) the complex formed between a hexameric protein Hfq and mRNA; and (iv) synthetic 'bottlebrush' polymers.

CcpNmr AnalysisAssign: a flexible platform for integrated NMR analysis.

NMR spectroscopy is an indispensably powerful technique for the analysis of biomolecules under ambient conditions, both for structural- and functional studies. However, in practice the complexity of the technique has often frustrated its application by non-specialists. In this paper, we present CcpNmr version-3, the latest software release from the Collaborative Computational Project for NMR, for all aspects of NMR data analysis, including liquid- and solid-state NMR data. This software has been designed to be simple, functional and flexible, and aims to ensure that routine tasks can be performed in a straightforward manner. We have designed the software according to modern software engineering principles and leveraged the capabilities of modern graphics libraries to simplify a variety of data analysis tasks. We describe the process of backbone assignment as an example of the flexibility and simplicity of implementing workflows, as well as the toolkit used to create the necessary graphics for this workflow. The package can be downloaded from www.ccpn.ac.uk/v3-software/downloads and is freely available to all non-profit organisations.