Adenine deactivation in DNA resolved at the CASPT2//CASSCF/AMBER level Irene Conti, a Piero Altoè, a Marco Stenta, a Marco Garavelli,* a and Giorgio Orlandi* a,b a Dipartimento di Chimica "G. Ciamician", Università di Bologna, via Selmi 2, Bologna, I-40126 Italy. b INSTM, UdR Bologna, Italy marco.garavelli@unibo.it; giorgio.orlandi@unibo.it Supporting Information S1. The QM/MM method We have developed a new code based on an hybrid Quantum Mechanical/Molecular Mechanical potential (QM/MM) 1 to study the chemical and photo-chemical reactivity of large systems. The method (called COBRAMM) has been presented in detail elsewhere 2 and it is briefly described here. Following our approach we divide the system into three layers (high, medium and low) as depicted in Figure S1 by adopting a hydrogen atom-link scheme 3 (i.e. free valences of the high (QM) layer are saturated with hydrogen atoms to give model-H, see Figure S1). Energies and forces of the high layer are computed at the QM level with an electrostatic embedding scheme to account for the electrostatic influence of the surrounding MM region on the QM (high) layer. That is, QM computation are performed on model-H surrounded by the atomic point charges of the MM layers (i.e. the emb charges). In our notation pod and emb are two subsets of atomic point charges of the MM region, see Figure S1. The medium and low layers are treated at the MM level and, analogously, the effect of charge changes occurring during the (photo)chemical process in the high (QM) layer is accounted for by using in the MM calculations the QM atomic point charges coming from QM computations. The energy values for the QM and MM region are added together to compute the correct QM/MM energy, and a subtractive scheme similar to ONIOM 4 is used for this purpose: E tot = E QM model " H + E MM real + E QM el. model " H/emb " E MM el. model/pod " E MM model " H The cartesian forces of the two regions are merged, then the total QM/MM energy and forces are transferred to an accurate optimization algorithm. In our code the high-medium layers are simultaneously optimized using the BFGS algorithm, 4 while the low region may be kept frozen or be fully optimized at each optimization step with a fast and rough algorithm, e.g. steepest descent (this feature nearly resembles the so called “micro-iteration” technique of ONIOM) 4 . The capability of handling coupled together the high-medium region allows the explicit treatment of large molecular motions around the reactive region without increasing the computational cost, because energy and forces of non-reacting (MM) atoms included in the medium region are computed at the MM level. The hydrogen atom-link approach is adopted to handle the boundary region between the QM and MM sub-systems. Supplementary Material for PCCP This journal is © The Owner Societies 2010