Molecular dynamics simulation of intrinsically disordered proteins

Abstract

Intrinsically disordered proteins are biomolecules that do not have a definite 3D structure; therefore, their dynamical simulation cannot start from a known list of atomistic positions, such as a Protein Data Bank file. We describe a method to start a computer simulation of these proteins. The first step of the procedure is the creation of a multi-rod configuration of the molecule, derived from its primary sequence. This structure is dynamically evolved in vacuo until its gyration radius reaches the experimental average value; at this point solvent molecules, in explicit or implicit implementation, are added to the protein and a regular molecular dynamics simulation follows. We have applied this procedure to the simulation of tau, one of the largest totally disordered proteins.

Keywords:

• molecular dynamics
• intrinsically disordered proteins
• tau protein

Acknowledgements

The authors thank Dr Gabriele Ciasca, Dr Giovanni Garberoglio and Dr Alessandro Grottesi for useful discussions.

Notes

1. www.uniprot.org/uniprot/P10636.

2. For the hexapeptide VQIVYK the pdb entries are 2ON9 and 3FQP.

3. GROMACS release 4.5.3, www.gromacs.org; box volume = 15253 nm³; ffamber99 force field; spce water model; time step 2 fs; modified Berendsen thermostat, Parrinello–Rahman pressure coupling.