Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
J Chem Theory Comput. 2022 Apr 12;18(4):2033-2041. doi: 10.1021/acs.jctc.1c01042. Epub 2022 Apr 4.
Coarse-grained molecular dynamics simulations are a useful tool to determine conformational ensembles of proteins. Here, we show that the coarse-grained force field Martini 3 underestimates the global dimensions of intrinsically disordered proteins (IDPs) and multidomain proteins when compared with small-angle X-ray scattering (SAXS) data and that increasing the strength of protein-water interactions favors more expanded conformations. We find that increasing the strength of interactions between protein and water by ca. 10% results in improved agreement with the SAXS data for IDPs and multidomain proteins. We also show that this correction results in a more accurate description of self-association of IDPs and folded proteins and better agreement with paramagnetic relaxation enhancement data for most IDPs. While simulations with this revised force field still show deviations to experiments for some systems, our results suggest that it is overall a substantial improvement for coarse-grained simulations of soluble proteins.
粗粒化分子动力学模拟是确定蛋白质构象的有用工具。在这里，我们表明，与小角 X 射线散射 (SAXS) 数据相比，粗粒化力场 Martini 3 低估了固有无序蛋白质 (IDP) 和多结构域蛋白质的整体尺寸，并且增加蛋白质-水相互作用的强度有利于更扩展的构象。我们发现，将蛋白质与水之间的相互作用强度提高约 10%，可使 IDP 和多结构域蛋白质与 SAXS 数据的一致性更好。我们还表明，这种校正可更准确地描述 IDP 的自组装和折叠蛋白质，并与大多数 IDP 的顺磁弛豫增强数据更好地吻合。虽然使用此修正力场的模拟对于某些系统仍然存在与实验的偏差，但我们的结果表明，对于可溶性蛋白质的粗粒化模拟，它总体上是一个重大改进。
