MacAinsh, M. | Search bioRxiv

bioRxiv2022

Sequence-Dependent Backbone Dynamics of Intrinsically Disordered Proteins

For intrinsically disordered proteins (IDPs), a pressing question is how sequence codes for function. Dynamics serves as a crucial link, reminiscent of the role of structure in sequence-function relations of structured proteins. To define general rules governing sequence-dependent backbone dynamics, we carried out long molecular dynamics simulations of eight IDPs. Blocks of residues exhibiting large amplitudes in slow dynamics are rigidified by local inter-residue interactions or secondary structures. A long region or an entire IDP can be slowed down by long-range contacts or secondary- structure packing. On the other hand, glycines promote fast dynamics and either demarcate rigid blocks or facilitate multiple modes of local and long-range inter-residue interactions. The sequence-dependent backbone dynamics endows IDPs with versatile response to binding partners, with some blocks recalcitrant while others readily adapting to intermolecular interactions.

biophysics↗

bioRxiv2021

Removing Thermostat Distortions of Protein Dynamics in Constant-Temperature Molecular Dynamics Simulations

Molecular dynamics simulations are widely used to determine equilibrium and dynamic properties of proteins. Nearly all simulations nowadays are carried out at constant temperature, with a Langevin thermostat among the most widely used. Thermostats distort protein dynamics, but whether or how such distortions can be corrected has long been an open question. Here we show that constant-temperature simulations with a Langevin thermostat dilate protein dynamics and present a correction scheme to remove the dynamic distortions. Specifically, ns-scale time constants for overall rotation are dilated significantly but sub-ns time constants for internal motions are dilated modestly, while all motional amplitudes are unaffected. The correction scheme involves contraction of the time constants, with the contraction factor a linear function of the time constant to be corrected. The corrected dynamics of eight proteins are validated by NMR data for rotational diffusion and for backbone amide and side-chain methyl relaxation. The present work demonstrates that, even for complex systems like proteins with dynamics spanning multiple timescales, one can predict how thermostats distort protein dynamics and remove such distortions. The correction scheme will have wide applications, facilitating force-field parameterization and propelling simulations to be on par with NMR and other experimental techniques in determining dynamic properties of proteins. TOC graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/447619v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@1aa72e8org.highwire.dtl.DTLVardef@15e0a4eorg.highwire.dtl.DTLVardef@f6c41borg.highwire.dtl.DTLVardef@c4e8e8_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗