title: Atomistic modelling of scattering data in the Collaborative Computational Project for Small Angle Scattering (CCP-SAS).
abstract: 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 whichGenAppprovides the deployment infrastructure for running applications on both standard and high-performance computing hardware, andSASSIEprovides 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.GenAppproduces the accessible web-based front end termedSASSIE-web, andGenAppandSASSIEalso 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.
authors.affiliation: Department of Structural and Molecular Biology, University College London , Darwin Building, Gower Street, London WC1E 6BT, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Perkins
authors.affiliation: Department of Structural and Molecular Biology, University College London , Darwin Building, Gower Street, London WC1E 6BT, UK.
authors.forename: David W
authors.initials: DW
authors.lastname: Wright
authors.affiliation: Center for Neutron Research, National Institute of Standards and Technology , Gaithersburg, MD 20899-8562, USA.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center at San Antonio , San Antonio, TX 78229-3900, USA.
authors.forename: Emre H
authors.initials: EH
authors.lastname: Brookes
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Kansas State University , Manhattan, KS 66506, USA.
authors.forename: Jianhan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Biology, Illinois Institute of Technology , 3101 S. Dearborn, Chicago, IL 60616, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Irving
authors.affiliation: Center for Neutron Research, National Institute of Standards and Technology , Gaithersburg, MD 20899-8562, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Krueger
authors.affiliation: Pharmacy Department, Franklin-Wilkins Building, King's College London , 150 Stamford Street, London SE1 9NH, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Barlow
authors.affiliation: Department of Chemistry, University of Bath , Claverton Down, Bath BA2 7AY, UK.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Edler
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD, UK; Research Complex at Harwell, STFC Rutherford Appleton Laboratory, Harwell Campus, Didcot, Oxfordshire OX11 0FA, UK; ISIS Facility, STFC Rutherford Appleton Laboratory, Harwell Campus, Didcot, Oxfordshire OX11 0QX, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Scott
authors.affiliation: Diamond Light Source Ltd , Diamond House, Harwell Science and Innovation Campus, Chilton, Didcot, Oxfordshire OX11 0DE, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Terrill
authors.affiliation: ISIS Facility, STFC Rutherford Appleton Laboratory, Harwell Campus , Didcot, Oxfordshire OX11 0QX, UK.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: King
authors.affiliation: Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899-8562, USA; Department of Chemistry, The University of Tennessee, Knoxville, TN 37996-1600, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Butler
authors.affiliation: Center for Neutron Research, National Institute of Standards and Technology , Gaithersburg, MD 20899-8562, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Curtis
keywords: molecular dynamics (MD); molecular modelling; scattering curve fits; small-angle-X-ray scattering (SAXS); small-angle-neutron scattering (SANS)