Benchmarking Hybrid Atomistic/Coarse-Grained Schemes for Proteins with an Atomistic Water Layer

Abstract

An approach to overcome the limited time and spatial scales in molecular dynamics (MD) simulations is to reduce the number of degrees of freedom in the system through coarse-graining. In hybrid atomistic/coarse-grained (AT/CG) simulations, the region of interest (e.g., the solute) is simulated at a higher level of resolution than the surrounding solvent. Recently, we have reparametrized the interactions between the GROMOS 54A7 force field and the GROMOS CG water model to correctly reproduce solvation free energies of side-chain analogues. In this study, a benchmarking of the AT-CG parametrization using a broad set of 22 proteins is conducted. On the basis of the results, the idea of introducing a thin AT water layer around the solute (protein) is revisited to provide a detailed first solvation shell. Different layer schemes were investigated: (a) the water molecules in the AT water layer around the whole protein were restrained to their respective closest protein atom, and (b) the AT water layer was present only around the charged side chains. Results show that the second scheme is more robust in practice and reduces artifacts from the hybrid model with only a small additional computational cost. In general, this layer scheme was found to preserve the structural properties of the proteins better compared to direct solvation in CG water.

Exploring the structure and dynamics of proteins in soil organic matter

“…Moreover, the average RMSD of spitz did not significantly deviate from the value observed in H 2 O in any of the tested conditions. The highest average RMSD of spitz was observed in SOM‐10 (0.38 ± 0.15 compared with 0.20 ± 0.03 in H 2 O and 0.26 ± 0.06 from literature 40 ), where also the highest conformational variability ( D HES ) was found. In Figure 3A (bottom panel) and 3C , the secondary structure assignments and the molecular conformation of the endpoints of the simulation trajectories of spitz in SOM‐10 are shown.…”

Simulation of aqueous solutes using the adaptive solvent-scaling (AdSoS) scheme

“…hydrated macromolecule or lipid bilayer), a particularly interesting combination of this type relies on embedding the FG solute in a FG solvent region itself surrounded by a CG solvent region, the two regions being separated by a buffer layer permitting FG↔CG mixing or interconversion. 16,[20][21][22][23][24][25][26][27][28][29][30] On the one hand, this combination provides a much more accurate FG treatment of short-range solvation compared to a direct solvation of the FG solute in the CG solvent 20,24,25,[31][32][33][34][35][36][37][38][39][40][41] . On the other hand, it is expected to retain most of the efficiency gain associated with a CG resolution of the solvent considering that solvent-solvent interactions in the bulk are typically determinant in terms of computational costs.…”

“…In the mixed-resolution variant, the FG and CG molecules are allowed to mix in the buffer layer. [20][21][22][24][25][26] The extent of mixing is typically controlled by means of attractive and/or repulsive restraints relative to the solute. In the adaptive-resolution variant, [27][28][29][30] the FG and CG particles interconvert into each other as they cross the buffer layer.…”