Biology subjects

Mazarakos, K.

Publications and source records attributed to Mazarakos, K..

3 recordsLinked to original sources

bioRxiv2022

SpiDec: Computing Binodals and Interfacial Tension of Biomolecular Condensates From Simulations of Spinodal Decomposition

Phase separation of intrinsically disordered proteins (IDPs) is a phenomenon associated with many essential cellular processes, but a robust method to compute the binodal from molecular dynamics simulations of IDPs modeled at the all-atom level in explicit solvent is still elusive, due to the difficulty in preparing a suitable initial dense configuration and in achieving phase equilibration. Here we present SpiDec as such a method, based on spontaneous phase separation via spinodal decomposition that produces a dense slab when the system is initiated at a homogeneous, low density. After illustrating the method on four model systems, we apply SpiDec to a tetrapeptide modeled at the all-atom level and solvated in TIP3P water. The concentrations in the dense and dilute phases agree qualitatively with experimental results and point to binodals as a sensitive property for force-field parameterization. SpiDec may prove useful for the accurate determination of the phase equilibrium of IDPs. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/496322v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@118b545org.highwire.dtl.DTLVardef@124e03eorg.highwire.dtl.DTLVardef@1fe3c5forg.highwire.dtl.DTLVardef@2dbc77_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2021

Multiphase Organization Is a Second Phase Transition Within Multi-Component Biomolecular Condensates

We present a mean-field theory for the multiphase organization of multi-component biomolecular condensates and validate the theory by molecular dynamics simulations of model mixtures. A first phase transition results in the separation of the dense phase from the bulk phase. In a second phase transition, the components in the dense phase demix to localize in separate regions that attach to each other. The second phase transition occurs when the strength of cross-species attraction goes below the mean strength of the self-attraction of the individual species and reaches a critical value. At a given strength of cross-species attraction, both of the phase transitions can be observed by decreasing temperature, leading first to phase separation and then to demixing of the dense phase. The theory and simulations establish the disparity in strength between self and cross-species attraction as a main driver for the multiphase organization of multi-component biomolecular condensates. TOC GRAPHICS O_FIG O_LINKSMALLFIG WIDTH=196 HEIGHT=200 SRC="FIGDIR/small/460104v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@e17fdcorg.highwire.dtl.DTLVardef@9168deorg.highwire.dtl.DTLVardef@7c07bcorg.highwire.dtl.DTLVardef@e0077d_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2021

Macromolecular Regulators Have Matching Effects on the Phase Equilibrium and Interfacial Tension of Biomolecular Condensates

The interfacial tension of phase-separated biomolecular condensates affects their fusion and multiphase organization, and yet how this important property depends on the composition and interactions of the constituent macromolecules is poorly understood. Here we use molecular dynamics simulations to determine the interfacial tension and phase equilibrium of model condensate-forming systems. The model systems consist of binary mixtures of Lennard-Jones particles or chains of such particles. We refer to the two components as drivers and regulators; the former has stronger self-interactions and hence a higher critical temperature (Tc) for phase separation. In previous work, we have shown that, depending on the relative strengths of driver-regulator interactions and driver-driver interactions, regulators can either promote or suppress phase separation (i.e., increase or decrease Tc). Here we find that the effects of regulators on Tc quantitatively match the effects on interfacial tension ({gamma}). This important finding means that, when a condensate-forming system experiences a change in macromolecular composition or a change in intermolecular interactions (e.g., by mutation or posttranslational modification, or by variation in solvent conditions such as temperature, pH, or salt), the resulting change in Tc can be used to predict the change in{gamma} and vice versa. We also report initial results showing that disparity in intermolecular interactions drives multiphase coexistence. These findings provide much needed guidance for understanding how biomolecular condensates mediate cellular functions.

biophysics↗