Studies on Molecular Dynamics of Intrinsically Disordered Proteins and Their Fuzzy Complexes: A Mini-Review

Abstract

The molecular dynamics (MD) method is a promising approach toward elucidating the molecular mechanisms of intrinsically disordered regions (IDRs) of proteins and their fuzzy complexes . This mini-review introduces recent studies that apply MD simulations to investigate the molecular recognition of IDRs. Firstly, methodological issues by which MD simulations treat IDRs, such as developing force fields, treating periodic boundary conditions, and enhanced sampling approaches, are discussed. Then, several examples of the applications of MD to investigate molecular interactions of IDRs in terms of the two kinds of complex formations; c oupled-folding and binding and fuzzy complex. MD simulations provide insight into the molecular mechanisms of these binding processes by sampling conformational ensembles of flexible IDRs. In particular, we focused on all-atom explicit-solvent MD simulations except for studies of higher-order assembly of IDRs. Recent advances in MD methods, and computational power make it possible to dissect the molecular details of realistic molecular systems involving the dynamic behavior of IDRs.

Computational strategy for intrinsically disordered protein ligand design leads to the discovery of p53 transactivation domain I binding compounds that activate the p53 pathway

“…We further performed MD simulations to gain insight into the binding features of p53 TAD1 and 1047. Given that force fields originally developed for ordered proteins are insufficient in sampling IDPs, 48,49 we firstly tested the newly developed force fields and water models parameterized for IDPs to better sample disordered p53 TAD1 ensemble. RSFF2 was developed by modifying the Amber ff99SB force field based on conformational free-energy distribution of the 20 amino acid residues from a protein coil library.…”

myPresto/omegagene 2020: a molecular dynamics simulation engine for virtual-system coupled sampling

“…Applications of the coarse-grained model to inves­tigate higher-order molecular assemblies are partially intro­ duced in Ref. [ 43 ], and their details are presented elsewhere.…”

Tumor‐Suppressor p53TAD1–60 Forms a Fuzzy Complex with Metastasis‐Associated S100A4: Structural Insights and Dynamics by an NMR/MD Approach

“…Clustering of conformations was carried out based on the main‐chain conformation of p53TAD 2–60 in the last 300 ns of the simulations using a cutoff of 1.0 Å. The applied forcefield in combination with a four‐point water model (OPC waters – in this study) was shown to correctly reproduce the SAXS profiles of systems with extreme flexibility [54] …”

“…The applied forcefield in combination with a four-point water model (OPC waters -in this study) was shown to correctly reproduce the SAXS profiles of systems with extreme flexibility. [54]…”