Integrating an Enhanced Sampling Method and Small-Angle X-Ray Scattering to Study Intrinsically Disordered Proteins

Intrinsically disordered proteins (IDPs) have been paid more and more attention over the past decades because they are involved in a multitude of crucial biological functions. Despite their functional importance, IDPs are generally difficult to investigate because they are very flexible and lack stable structures. Computer simulation may serve as a useful tool in studying IDPs. With the development of computer software and hardware, computational methods, such as molecular dynamics (MD) simulations, are popularly used. However, there is a sampling problem in MD simulations. In this work, this issue is investigated using an IDP called unique long region 11 (UL11), which is the conserved outer tegument component from herpes simplex virus 1. After choosing a proper force field and water model that is suitable for simulating IDPs, an integrative modeling by combining an enhanced sampling method and experimental data like small-angle X-ray scattering (SAXS) is utilized to efficiently sample the conformations of UL11. The simulation results are in good agreement with experimental data. This work may provide a general protocol to study structural ensembles of IDPs.