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

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...

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Bibliographic Details
Published inLife (Basel, Switzerland) Vol. 10; no. 7; p. 109
Main Authors Sullivan, Sandra S., Weinzierl, Robert O.J.
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 10.07.2020
MDPI
Subjects
Accuracy
Amino acid sequence
Amino acids
Apoptosis
Bias
c-MYC
c-Myc protein
Cell proliferation
Computer applications
Computer simulation
Fluid dynamics
Hydrogen bonds
Molecular dynamics
molecular dynamics simulations
Molecular modelling
Myc protein
NMR
Nuclear magnetic resonance
oncoproteins
Optimization
Physical simulation
Principal components analysis
Probability distribution
Protein structure
Proteins
Secondary structure
Simulation
Solvation
Solvents
Structure-function relationships
Trajectory analysis
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Summary: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.
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ISSN:2075-1729
2075-1729
DOI:10.3390/life10070109