caa a22 4500 605510733 CHVBK 20210128100647.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00894-014-2556-2 doi (NATIONALLICENCE)springer-10.1007/s00894-014-2556-2 Modeling the antiferromagnetic MnIIMnII system within the protein phosphatase-5 catalytic site [Elektronische Daten] [E. Salter, R. Honkanen, A. Wierzbicki] Protein phosphatase-5 (PP5), a novel target for inhibition in a search for new antitumor drugs, contains a homobimetallic MnIIMnII system in its catalytic site. The ground electronic state is an antiferromagnetically-coupled singlet. We report optimizations of a known inhibitor within a 42-residue model of the PP5 catalytic site under several two-level hybrid ONIOM computational models. Using the high-resolution crystal structure of a PP5/inhibitor complex as reference, we compare geometric parameters as the qualities of the "high-level” and "low-level” wavefunctions are successively improved by using the correct antiferromagnetic (AF) singlet state. We find that the UB3LYP AF wavefunction for the high-level region is necessary for experimental fidelity. A closed-shell semi-empirical method (RPM6) can be used for the low-quality part of the hybrid scheme to afford geometries which are qualitatively on par with that obtained using the more time-consuming open-shell UB3LYP AF wavefunction. As the AF state can be elusive for such a large system, the ferromagnetic (F) state can also be used in the low-quality calculations without impacting the geometry. Springer-Verlag Berlin Heidelberg, 2015 Antiferromagnetic bimetal system nationallicence DFT nationallicence Enzyme-inhibitor interactions nationallicence ONIOM nationallicence Protein phosphatase-5 nationallicence Salter E. Department of Chemistry, University of South Alabama, 36688, Mobile, AL, USA aut Honkanen R. Department of Biochemistry & Molecular Biology, University of South Alabama, 36688, Mobile, AL, USA aut Wierzbicki A. Department of Chemistry, University of South Alabama, 36688, Mobile, AL, USA aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/1(2015-01-01), 1-5 1610-2940 21:1<1 2015 21 894 https://doi.org/10.1007/s00894-014-2556-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-014-2556-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Salter E. Department of Chemistry, University of South Alabama, 36688, Mobile, AL, USA aut NATIONALLICENCE 700 1- Honkanen R. Department of Biochemistry & Molecular Biology, University of South Alabama, 36688, Mobile, AL, USA aut NATIONALLICENCE 700 1- Wierzbicki A. Department of Chemistry, University of South Alabama, 36688, Mobile, AL, USA aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/1(2015-01-01), 1-5 1610-2940 21:1<1 2015 21 894