Free-energy landscape of intrinsically disordered proteins investigated by all-atom multicanonical molecular dynamics.
We introduce computational studies on intrinsically disordered proteins (IDPs). Especially, we present our multicanonical molecular dynamics (McMD) simulations of two IDP-partner systems: NRSF-mSin3 and pKID-KIX. McMD is one of enhanced conformational sampling methods useful for conformational sampling of biomolecular systems. IDP adopts a specific tertiary structure upon binding to its partner molecule, although it is unstructured in the unbound state (i.e. the free state). This IDP-specific property is called "coupled folding and binding". The McMD simulation treats the biomolecules with an all-atom model immersed in an explicit solvent. In the initial configuration of simulation, IDP and its partner molecules are set to be distant from each other, and the IDP conformation is disordered. The computationally obtained free-energy landscape for coupled folding and binding has shown that native- and non-native-complex clusters distribute complicatedly in the conformational space. The all-atom simulation suggests that both of induced-folding and population-selection are coupled complicatedly in the coupled folding and binding. Further analyses have exemplified that the conformational fluctuations (dynamical flexibility) in the bound and unbound states are essentially important to characterize IDP functioning.
Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan, higo@protein.osaka-u.ac.jp.
Junichi
J
Higo
Koji
K
Umezawa
D001665:Binding Sites; D050882:CREB-Binding Protein / Q000737:chemistry*; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry*; D006655:Histone Deacetylases / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D008024:Ligands; D050882:CREB-Binding Protein; D006655:Histone Deacetylases