The Effect of Macromolecular Crowding on the Electrostatic Component of Barnase–Barstar Binding: A Computational, Implicit Solvent-Based Study
Helena W. Qi
Priyanka Nakka
Connie Chen
Mala L. Radhakrishnan
10.1371/journal.pone.0098618
https://plos.figshare.com/articles/dataset/_The_Effect_of_Macromolecular_Crowding_on_the_Electrostatic_Component_of_Barnase_8211_Barstar_Binding_A_Computational_Implicit_Solvent_Based_Study_/1052251
<div><p>Macromolecular crowding within the cell can impact both protein folding and binding. Earlier models of cellular crowding focused on the excluded volume, entropic effect of crowding agents, which generally favors compact protein states. Recently, other effects of crowding have been explored, including enthalpically-related crowder–protein interactions and changes in solvation properties. In this work, we explore the effects of macromolecular crowding on the electrostatic desolvation and solvent-screened interaction components of protein–protein binding. Our simple model enables us to focus exclusively on the electrostatic effects of water depletion on protein binding due to crowding, providing us with the ability to systematically analyze and quantify these potentially intuitive effects. We use the barnase–barstar complex as a model system and randomly placed, uncharged spheres within implicit solvent to model crowding in an aqueous environment. On average, we find that the desolvation free energy penalties incurred by partners upon binding are lowered in a crowded environment and solvent-screened interactions are amplified. At a constant crowder density (fraction of total available volume occupied by crowders), this effect generally increases as the radius of model crowders decreases, but the strength and nature of this trend can depend on the water probe radius used to generate the molecular surface in the continuum model. In general, there is huge variation in desolvation penalties as a function of the random crowder positions. Results with explicit model crowders can be qualitatively similar to those using a lowered “effective” solvent dielectric to account for crowding, although the “best” effective dielectric constant will likely depend on multiple system properties. Taken together, this work systematically demonstrates, quantifies, and analyzes qualitative intuition-based insights into the effects of water depletion due to crowding on the electrostatic component of protein binding, and it provides an initial framework for future analyses.</p></div>
2014-06-10 03:06:10
Biochemistry
Biochemical simulations
Biomacromolecule-ligand interactions
Protein chemistry
biophysics
Biophysical simulations
cell biology
Molecular cell biology
Computational biology
molecular biology
Macromolecular structure analysis
Macromolecular complex analysis
Theoretical biology
chemistry
computational chemistry
Molecular mechanics
Chemical physics
Physical chemistry
Theoretical chemistry
physics
thermodynamics
macromolecular
crowding
electrostatic
implicit
solvent-based