RESUMEN
The molecular dynamics (MD) method is a promising approach for investigating the molecular mechanisms of microscopic phenomena. In particular, generalized ensemble MD methods can efficiently explore the conformational space with a rugged free-energy surface. However, the implementation and acquisition of technical knowledge for each generalized ensemble MD method are not straightforward for end-users. Here, we present a new version of the myPresto/omegagene software, which is an MD simulation engine tailored for a series of generalized ensemble methods, which are virtual-system coupled multicanonical MD (V-McMD), virtual-system coupled adaptive umbrella sampling (V-AUS), and virtual-system coupled canonical MD (VcMD). This program has been applied in several studies analyzing free-energy landscapes of a variety of molecular systems with all-atom simulations. The updated version provides new functionality for coarse-grained simulations powered by the hydrophobicity scale method. The software package includes a step-by-step tutorial document for enhanced conformational sampling of the poly-glutamine (poly-Q) oligomer expressed as a one-bead per residue model. The myPresto/omegagene software is freely available at the following URL: https://github.com/kotakasahara/omegagene under the Apache2 license.
RESUMEN
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; coupled-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.