SASSIE: A program to study intrinsically disordered biological molecules and macromolecular ensembles using experimental scattering restraints

Abstract A program to construct ensembles of biomolecular structures that are consistent with experimental scattering data are described. Specifically, we generate an ensemble of biomolecular structures by varying sets of backbone dihedral angles that are then filtered using experimentally determined restraints to rapidly determine structures that have scattering profiles that are consistent with scattering data. We discuss an application of these tools to predict a set of structures for the HIV-1 Gag protein, an intrinsically disordered protein, that are consistent with small-angle neutron scattering experimental data. We have assembled these algorithms into a program called SASSIE for structure generation, visualization, and analysis of intrinsically disordered proteins and other macromolecular ensembles using neutron and X-ray scattering restraints. Program summary Program title: SASSIE Catalogue identifier: AEKL_v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AEKL_v1_0.html Program obtainable from: CPC Program Library, Queenʼs University, Belfast, N. Ireland Licensing provisions: GNU General Public License v3 No. of lines in distributed program, including test data, etc.: 3 991 624 No. of bytes in distributed program, including test data, etc.: 826 Distribution format: tar.gz Programming language: Python, C/C++, Fortran Computer: PC/Mac Operating system: 32- and 64-bit Linux (Ubuntu 10.04, Centos 5.6) and Mac OS X (10.6.6) RAM: 1 GB Classification: 3 External routines: Python 2.6.5, numpy 1.4.0, swig 1.3.40, scipy 0.8.0, Gnuplot-py-1.8, Tcl 8.5, Tk 8.5, Mac installation requires aquaterm 1.0 (or X window system) and Xcode 3 development tools. Nature of problem: Open source software to generate structures of disordered biological molecules that subsequently allow for the comparison of computational and experimental results is limiting the use of scattering resources. Solution method: Starting with an all atom model of a protein, for example, users can input regions to vary dihedral angles, ensembles of structures can be generated. Additionally, simple two-body rigid-body rotations are supported with and without disordered regions. Generated structures can then be used to calculate small-angle scattering profiles which can then be filtered against experimentally determined data. Filtered structures can be visualized individually or as an ensemble using density plots. In the modular and expandable program framework the user can easily access our subroutines and structural coordinates can be easily obtained for study using other computational physics methods. Additional comments: The distribution file for this program is over 159 Mbytes and therefore is not delivered directly when download or Email is requested. Instead an html file giving details of how the program can be obtained is sent. Running time: Varies depending on application. Typically 10 minutes to 24 hours depending on the number of generated structures. References: [1] M.S. Kent, J.K. Murton, S. Satija, B. Akgun, H. Nanda, J.E. Curtis, J. Majewski, J.R. Engen, C.R. Morgan, Neutron reflectivity study of the conformation of HIV nef bound to lipid membranes, Biophys. J. 99 (6) (2010) 1940–1948. [2] H. Nanda, S.A.K. Datta, F. Heinrich, M. Losche, A. Rein, S. Krueger, J.E. Curtis, Electrostatic interactions and binding orientation of HIV-1 matrix, studied by neutron reflectivity, Biophys. J. 99 (7) (2010) 2516–2524. [3] S.A.K. Datta, J.E. Curtis, W. Ratcli, P.K. Clark, R.M. Crist, J. Lebowitz, S. Krueger, A. Rein, Conformation of the HIV-1 Gag protein in solution, J. Mol. Biol. 365 (3) (2007) 812–824.