Reduced Point Charge Models of Proteins: Effect of Protein–Water Interactions in Molecular Dynamics Simulations of Ubiquitin Systems

We
investigate the influence of various solvent models on the structural
stability and protein–water interface of three ubiquitin complexes
(PDB access codes: 1Q0W, 2MBB, 2G3Q) modeled using the
Amber99sb force field (FF) and two different point charge distributions.
A previously developed reduced point charge model (RPCM), wherein
each amino acid residue is described by a limited number of point
charges, is tested and compared to its all-atom (AA) version. The
complexes are solvated in TIP4P-Ew or TIP3P type water molecules,
involving either the scaling of the Lennard-Jones protein–Owater interaction parameters, or the coarse-grain (CG) SIRAH
water description. The best agreements between the RPCM and AA models
were obtained for structural, protein–water, and ligand–ubiquitin
properties when using the TIP4P-Ew water FF with a scaling factor
γ of 0.7. At the RPCM level, a decrease in γ, or the inclusion
of SIRAH particles, allows weakening of the protein–water interactions.
It results in a slight collapse of the protein structure and a less
compact hydration shell and, thus, in a decrease in the number of
protein–water and water–water H-bonds. The dynamics
of the surface protein atoms and of the water shell molecules are
also slightly refrained, which allow the generation of stable RPCM
trajectories.