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Within molecular dynamics simulations of protein–solvent systems the exact evaluation of long-range Coulomb interactions is computationally demanding and becomes prohibitive for large systems. Conventional truncation methods circumvent that computational problem, but are hampered by serious artifacts concerning structure and dynamics of the simulated systems. To avoid these artifacts we have developed an efficient and yet sufficiently accurate approximation scheme which combines the structure-adapted multipole method (SAMM) [C. Niedermeier and P. Tavan, J. Chem. Phys., 101, 734 (1994)] with a multiple-time-step method. The computational effort for MD simulations required within our fast multiple-time-step structure-adapted multipole method (FAMUSAMM) scales linearly with the number of particles. For a system with 36,000 atoms we achieve a computational speed-up by a factor of 60 as compared with the exact evaluation of the Coulomb forces. Extended test simulations show that the applied approximations do not seriously affect structural or dynamical properties of the simulated systems.

Enoyl-CoA carboxylases/reductases (ECRs) are some of the most efficient CO2-fixing enzymes described to date. However, the molecular mechanisms underlying the extraordinary catalytic activity of ECRs on the level of the protein assembly remain elusive. Here we used a combination of ambient-temperature X-ray free electron laser (XFEL) and cryogenic synchrotron experiments to study the structural organization of the ECR from Kitasatospora setae. The K. setae ECR is a homotetramer that differentiates into a pair of dimers of open- and dosed-form subunits in the catalytically active state. Using molecular dynamics simulations and structure-based mutagenesis, we show that catalysis is synchronized in the K. setae ECR across the pair of dimers. This conformational coupling of catalytic domains is conferred by individual amino acids to achieve high CO2-fixation rates. Our results provide unprecedented insights into the dynamic organization and synchronized inter- and intrasubunit communications of this remarkably efficient CO2-fixing enzyme during catalysis., NSF Science and Technology Center Grant; Biology with X-ray Lasers, BioXFEL; Scientific and Technological Research Council of Turkey (TÜBİTAK); 2232 International Fellowship for Outstanding Researchers Program; 1001 Scientific and Technological Research Projects Funding Program; U.S. Department of Energy; Office of Science; Office of Basic Energy Sciences; European Union (EU); Horizon 2020 ; European Research Council (ERC); SYBORG; U.S. Department of Energy Joint Genome Institute; DOE Office of Science User Facility; Max Planck Society; a Max-Planck-Partner Group; CONICYT; CONICYT Doctorado Nacional Grant; Fondo Nacional de Desarrollo Científico y Tecnológico (Fondecyt) Postdoctoral Fellowship; DOE Office of Science, Biological Environmental Research; National Institutes of Health; National Science Foundation Major Research Instrument Grant; NIGMS; Stanford PRECOURT Institute