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

Abstract

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.

Adaptive resolution simulation of a biomolecule and its hydration shell: Structural and dynamical properties

“…However, sufficient detail must be retained in order to correctly describe physical or chemical processes of interest, and in heterogeneous systems, this can lead to a multiresolution scheme in which different parts of the system are simultaneously modelled at different levels of resolution. 5,6 In fully classical multiscale schemes, to which we restrict ourselves here, the boundaries between resolutions generally correspond to the boundaries between system components, i.e., the biomolecule of interest is modelled at one resolution, while the components of its environment, such as solvent, a) Electronic mail: fogarty@mpip-mainz.mpg.de b) Electronic mail: potestio@mpip-mainz.mpg.de c) Electronic mail: kremer@mpip-mainz.mpg.de lipid membranes, and other biomolecules, are each modelled at one or more different resolutions. The resolution of a given molecule then generally remains fixed for the entire duration of the simulation.…”

On Using Atomistic Solvent Layers in Hybrid All-Atom/Coarse-Grained Molecular Dynamics Simulations

“…However, we expect our results to be relevant also for the investigation of structural, dynamic, and thermodynamic properties of larger (biomolecular) solutes in similar AA/CG schemes, as well as for related triple-scale QM/MM/CG approaches. 55,56 In this context, we would also like to note in passing that processes in which the AA subsystem of interest significantly changes volume, such as a protein that undergoes large-scale conforma- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 which smoothens out the density profile across the AA/CG interface. In addition, a sufficiently large healing region ensures that artifacts due to orientational ordering of solvent molecules at the AA/CG boundary are negligible inside the inner, fully atomistic region.…”

Amide Rotation Hindrance Predicts Proteolytic Resistance of Cystine-Knot Peptides

“…In the high-resolution crystal structure of the binding complex formed by porcine β-trypsin with the MCTI-A inhibitor (PDB ID: 1MCT), 8 as shown in Figure S2, it interacts with trypsin active site like the corresponding hexapeptide substrate Cys3-Pro4-Arg5-Ile6-Trp7-Met8. Previously, we have studied the acylation reaction of the scissile bond between Arg5-Ile6 for the same trypsin-hexapeptide complex 21 by employing B3LYP/6-31+G* QM/MM MD simulations 17–18 with the pseudobond approach 22–24 . The calculated overall free energy barrier of 16.9 kcal/mol indicates that this hexapeptide can be easily acylated by porcine β-trypsin, consistent with other theoretical studies that this is a substrate.…”