Refined bonded terms in coarse-grained models for intrinsically disordered proteins improve backbone conformations

• Main Authors: Hu, Zixin, Sun, Tiedong, Chen, Wenwen, Nordenskiöld, Lars, Lu, Lanyuan
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2024
• Subjects: Medicine, Health and Life Sciences; Coarse-grained modeling; Intrinsically disordered proteins
• Online Access: https://hdl.handle.net/10356/180959
• Institution: Nanyang Technological University

Coarse-grained models designed for intrinsically disordered proteins and regions (IDP/Rs) usually omit some bonded potentials (e.g., angular and dihedral potentials) as a conventional strategy to enhance backbone flexibility. However, a notable drawback of this approach is the generation of inaccurate backbone conformations. Here, we addressed this problem by introducing residue-specific angular, refined dihedral, and correction map (CMAP) potentials, derived based on the statistics from a customized coil database. These bonded potentials were integrated into the existing Mpipi model, resulting in a new model, denoted as the "Mpipi+" model. Results show that the Mpipi+ model can improve backbone conformations. More importantly, it can markedly improve the secondary structure propensity (SSP) based on the experimental chemical shift and, consequently, succeed in capturing transient secondary structures. Moreover, the Mpipi+ model preserves the liquid-liquid phase separation (LLPS) propensities of IDPs.