期刊
MOLECULES
卷 27, 期 17, 页码 -出版社
MDPI
DOI: 10.3390/molecules27175726
关键词
molecular dynamics simulation; enhanced sampling method; molecular force fields; van der Waals interaction; CHARMM36m; NBFIX; intrinsically disordered proteins; crowding simulations
资金
- MEXT [JPMXP1020200101, JPMXP1020200201]
- MEXT Kakenhi [19H05645, 21H05249]
- RIKEN pioneering projects in Biology of Intracellular Environments, and Glycolipidologue
Proper balance between protein-protein and protein-water interactions is crucial for molecular dynamics simulations of proteins. Increasing the protein-water interactions helps optimize the balance and has significant effects on diffusive properties of proteins in crowded solutions.
Proper balance between protein-protein and protein-water interactions is vital for atomistic molecular dynamics (MD) simulations of globular proteins as well as intrinsically disordered proteins (IDPs). The overestimation of protein-protein interactions tends to make IDPs more compact than those in experiments. Likewise, multiple proteins in crowded solutions are aggregated with each other too strongly. To optimize the balance, Lennard-Jones (LJ) interactions between protein and water are often increased about 10% (with a scaling parameter, lambda = 1.1) from the existing force fields. Here, we explore the optimal scaling parameter of protein-water LJ interactions for CHARMM36m in conjunction with the modified TIP3P water model, by performing enhanced sampling MD simulations of several peptides in dilute solutions and conventional MD simulations of globular proteins in dilute and crowded solutions. In our simulations, 10% increase of protein-water LJ interaction for the CHARMM36m cannot maintain stability of a small helical peptide, (AAQAA)(3) in a dilute solution and only a small modification of protein-water LJ interaction up to the 3% increase (lambda = 1.03) is allowed. The modified protein-water interactions are applicable to other peptides and globular proteins in dilute solutions without changing thermodynamic properties from the original CHARMM36m. However, it has a great impact on the diffusive properties of proteins in crowded solutions, avoiding the formation of too sticky protein-protein interactions.
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