PUPIL: a Software Integration System for Multi- scale QM/MM-MD Simulations and its Application to Biomolecular Systems Juan Torras, 1 * B.P. Roberts, 2 G.M. Seabra, 3and S.B. Trickey 4 * 1Department of Chemical Engineering, EEI, Universitat Politècnica de Catalunya, Av. Pla de la Massa 8, Igualada 08700, Spain 2 Centre for eResearch, The University of Auckland, Private Bag 92019, Auckland 1142 New Zealand 3Departamento de Química Fundamental, Universidade Federal de Pernambuco, Cidade Universitária, Recife, Pernambuco CEP 50.740-540, Brazil 4Department of Physics, Department of Chemistry, and Quantum Theory Project, Univ. of Florida, Gainesville Florida 32611-8435, USA * Corresponding Authors:
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[email protected] 1 Abstract PUPIL (Program for User Package Interfacing and Linking) implements a distinctive multi-scale approach to hybrid quantum mechanical/molecular mechanical molecular dynamics (QM/MM-MD) simulations. Originally developed to interface different external programs for multi-scale simulation with applications in the materials sciences, PUPIL is finding increasing use in the study of complex biological systems. Advanced MD techniques from the external packages can be applied readily to a hybrid QM/MM treatment in which the forces and energy for the QM region can be computed by any of the QM methods available in any of the other external packages. Here we give a survey of PUPIL design philosophy, main features, and key implementation decisions, with an orientation to biomolecular simulation. We discuss recently implemented features which enable highly realistic simulations of complex biological systems which have more than one active site that must be treated concurrently.