scholarly journals Hierarchical Ensembles of Intrinsically Disordered Proteins at Atomic Resolution in Molecular Dynamics Simulations

2019 ◽  
Vol 16 (1) ◽  
pp. 725-737 ◽  
Author(s):  
Lisa M. Pietrek ◽  
Lukas S. Stelzl ◽  
Gerhard Hummer
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Intrinsically Disordered Proteins ◽  
Atomic Resolution ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Dynamics Simulations

scholarly journals Optimization of Molecular Dynamics Simulations of c-MYC1-88—An Intrinsically Disordered System

Life ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 109 ◽  
Author(s):  
Sandra S. Sullivan ◽  
Robert O.J. Weinzierl
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Proliferation And Apoptosis ◽  
Conventional Structure ◽  
Experimental Approaches ◽  
Dynamics Simulations

Many of the proteins involved in key cellular regulatory events contain extensive intrinsically disordered regions that are not readily amenable to conventional structure/function dissection. The oncoprotein c-MYC plays a key role in controlling cell proliferation and apoptosis and more than 70% of the primary sequence is disordered. Computational approaches that shed light on the range of secondary and tertiary structural conformations therefore provide the only realistic chance to study such proteins. Here, we describe the results of several tests of force fields and water models employed in molecular dynamics simulations for the N-terminal 88 amino acids of c-MYC. Comparisons of the simulation data with experimental secondary structure assignments obtained by NMR establish a particular implicit solvation approach as highly congruent. The results provide insights into the structural dynamics of c-MYC1-88, which will be useful for guiding future experimental approaches. The protocols for trajectory analysis described here will be applicable for the analysis of a variety of computational simulations of intrinsically disordered proteins.

scholarly journals Characterization of partially ordered states in the intrinsically disordered N-terminal domain of p53 using millisecond molecular dynamics simulations

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Pablo Herrera-Nieto ◽  
Adrià Pérez ◽  
Gianni De Fabritiis
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Intrinsically Disordered Proteins ◽  
Dynamical Behavior ◽  
Disordered Proteins ◽  
Partially Ordered ◽  
Intrinsically Disordered ◽  
State Models ◽  
Dynamics Simulations

Abstract The exploration of intrinsically disordered proteins in isolation is a crucial step to understand their complex dynamical behavior. In particular, the emergence of partially ordered states has not been explored in depth. The experimental characterization of such partially ordered states remains elusive due to their transient nature. Molecular dynamics mitigates this limitation thanks to its capability to explore biologically relevant timescales while retaining atomistic resolution. Here, millisecond unbiased molecular dynamics simulations were performed in the exemplar N-terminal region of p53. In combination with state-of-the-art Markov state models, simulations revealed the existence of several partially ordered states accounting for $$\sim $$ ∼ 40% of the equilibrium population. Some of the most relevant states feature helical conformations similar to the bound structure of p53 to Mdm2, as well as novel $$\beta $$ β -sheet elements. This highlights the potential complexity underlying the energy surface of intrinsically disordered proteins.

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