ARMOR: A Package for Accurate and Rapid Computation of Molecular Optimization Restraints Konstantin Berlin 1,2 , Nail A. Gumerov 2 , Ramani Duraiswami 2 , Theodore K. Dayie 1 , and David Fushman 1,2 1 Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Organization, University of Maryland, College Park, MD 20742, USA 2 Institute for Advanced Computer Studies, University of Maryland, College Park, MD 20742, USA We present ARMOR (Accurate and Rapid computation of Molecular Optimization Restraints) package for rapidly computing several important long-range molecular restraints used in multi-domain structural refinement of complexes consisting of DNA, RNA, and/or protein molecules. The package consists of three major toolboxes: (i) a package for processing nuclear spin-relaxation data (R 1 , R 2 , and NOE) and derivation of associated parameters, ab initio prediction of the rotational diffusion tensor, and rapid rigid-body docking based on these data; (ii) a package for processing, prediction, and docking based on Residual Dipolar Couplings (RDCs); and (iii) a high-performance parallelized (on CPU and GPU) computation package for ab initio prediction of Small-Angle Scattering (SAS) profile. Written mainly in Java, ARMOR can run on virtually any platform, including Linux, Windows, and Mac OS, and contains a highly scalable, thread-safe API (Application Programming Interface) that can be rapidly leveraged by advanced users for easy integration into their own software. The relaxation toolbox has several important capabilities. First, it consists of a new version of the ROTDIF program 1,2 , which can now simultaneously analyze relaxation data for 15 N and 13 C at several fields. The new ROTDIF 3.0 is orders of magnitude faster than the previous version, and is now able to accurately compute a fully anisotropic rotational diffusion tensor from a 250+ bond dataset in under 0.05 s, on a standard laptop. ROTDIF is also more robust, based on our simulations, when processing data with large conformational exchange contributions. Order parameters can also be rapidly computed. Finally, to improve accessibility to all the program features and simplify the user experience, we introduced a graphical user interface (GUI) that simplifies and speeds up the analysis of the data. The toolbox also contains ELM 3 and ELMDOCK 4 , a program for ab initio prediction of the rotational diffusion tensor from molecular structure, and the associated docking program that orients and docks a two-domain system based on relaxation data. The prediction can be computed in less than 0.1 s, and docking can be performed within a few seconds on a standard laptop. The RDC toolbox is similar in concept to the relaxation toolbox, and also consists of two main components. First, it contains a program that can compute molecular alignment tensor from 15 N and/or 13 C residual dipolar couplings. Second, it contains PATI 5 program that can quickly predict alignment tensor based on molecular shape for planar, steric alignment media. The prediction can be done in less than 0.1 s. This prediction algorithm is used in PATIDOCK 6 to rapidly (within a few seconds) align and dock a two-domain system based on its overall alignment tensor. The SAS toolbox consists of two major algorithms that we developed for rapid atomic level computation of the small-angle scattering profile (Debye summation). The first algorithm is a hierarchal spherical harmonic expansion and translation method 7 (based on a similar Fast Multipole Methods developed for acoustic scattering), which we have demonstrated to be asymptotically the fastest published algorithm for Debye summation. The second algorithm is based on GPU acceleration of Debye summations, which we demonstrated to give more than 30 times speedup over similar parallel CPU implementations, and is faster than the hierarchal method for smaller molecules. ARMOR can be used to rapidly determine a model of molecular interactions/arrangement with only a few sets of experimental data, as well as be integrated in a general docking algorithm, providing a unique set of long-range restraints to complement standard energy functions. ARMOR can be used for both protein and DNA/RNA analysis, and is under rapid development, with new GUI interfaces, and other new features in the process of being added. References: 1. O. Walker, R. Varadan, D. Fushman, J. Magn Reson 168 (2004) 336–345. 2. N. Eldho, K. Dayie, J. Mol Biol 365 (2007) 930–944. 3. Y. Ryabov, D. Fushman, J. Am Chem Soc 129 (2007) 7894–7902. 4. K. Berlin, D. P. O’Leary, D. Fushman, Proteins: Structure, Function, and Bioinformatics 79 (2011) 2268–2281. 5. K. Berlin, D.P. O’Leary, D. Fushman, J. Magn Reson 201 (2009) 25–33. 6. K. Berlin, D.P. O’Leary, D. Fushman, J. Am Chem Soc 132 (2010) 8961–8972. 7. N. Gumerov, K. Berlin, D. Fushman, R. Duraiswami. A hierarchical algorithm for fast Debye summation with applications to small angle scattering. Technical report, University of Maryland, 2011. Figure 1: A snapshot of ROTDIF 3.0 GUI.