Multi-Resolution Simulation of Biomolecular Systems: A Review of Methodological Issues

• Published in: Angewandte Chemie International Edition 2013-03, Vol.52 (10), p.2820-2834
• Main Authors: Meier, Katharina, Choutko, Alexandra, Dolenc, Jozica, Eichenberger, Andreas P., Riniker, Sereina, van Gunsteren, Wilfred F.
• Format: Article
• Language: English
• Subjects: Algorithms; Amino Acid Sequence; Catalysis; Catalysts; computational chemistry; Computer simulation; Crystallography, X-Ray; Degrees of freedom; Electronics; Enzymes; Illustrations; Mathematical analysis; Models, Biological; Molecular Dynamics Simulation; Molecular Sequence Data; protein modeling; Proteins - chemistry; Sequence Alignment; Studies; theoretical chemistry
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201205408

Theoretical‐computational modeling with an eye to explaining experimental observations in regard to a particular chemical phenomenon or process requires choices concerning essential degrees of freedom and types of interactions and the generation of a Boltzmann ensemble or trajectories of configurations. Depending on the degrees of freedom that are essential to the process of interest, for example, electronic or nuclear versus atomic, molecular or supra‐molecular, quantum‐ or classical‐mechanical equations of motion are to be used. In multi‐resolution simulation, various levels of resolution, for example, electronic, atomic, supra‐atomic or supra‐molecular, are combined in one model. This allows an enhancement of the computational efficiency, while maintaining sufficient detail with respect to particular degrees of freedom. The basic challenges and choices with respect to multi‐resolution modeling are reviewed and as an illustration the differential catalytic properties of two enzymes with similar folds but different substrates with respect to these substrates are explored using multi‐resolution simulation at the electronic, atomic and supra‐molecular levels of resolution. Various levels of resolution, for example, electronic, atomic, supramolecular, are combined in one model in multi‐resolution simulations. The basic choices when setting up a multi‐resolution model are reviewed. As an illustration the differential catalytic properties of two enzymes with similar folds are explored using multi‐resolution simulation at three different levels of resolution.