Electrostatic Interactions in Protein Structure, Folding, Binding, and Condensation

Abstract

Charged and polar groups, through forming ion pairs, hydrogen bonds, and other less specific electrostatic interactions, impart important properties to proteins. Modulation of the charges on the amino acids, e.g., by pH and by phosphorylation and dephosphorylation, have significant effects such as protein denaturation and switch-like response of signal transduction networks. This review aims to present a unifying theme among the various effects of protein charges and polar groups. Simple models will be used to illustrate basic ideas about electrostatic interactions in proteins, and these ideas in turn will be used to elucidate the roles of electrostatic interactions in protein structure, folding, binding, condensation, and related biological functions. In particular, we will examine how charged side chains are spatially distributed in various types of proteins and how electrostatic interactions affect thermodynamic and kinetic properties of proteins. Our hope is to capture both important historical developments and recent experimental and theoretical advances in quantifying electrostatic contributions of proteins.

Sequence-dependent correlated segments in the intrinsically disordered region of ChiZ

“…Sequence analysis and coarse-grained modeling have identified some generic determinants, in particular charged residues, for disorder and mean sizes of IDPs (16)(17)(18)(19). In recent years, small angle x-ray/neutron scattering (SAXS/SANS) (20), fluorescence techniques including nanosecond fluorescence correlation spectroscopy (nsFCS) and single-molecule fluorescence resonance energy transfer (smFRET) (21)(22)(23), nuclear magnetic resonance (NMR) spectroscopy (24), and all-atom molecular dynamics (MD) simulations (25) have become key biophysical tools to characterize conformation ensembles of IDPs.…”

What Are We Missing by Not Measuring the Net Charge of Proteins?

“…[1,4] Deoxyribonuclease and ovalbumin, for example, have identical isoelectricp oints of pI = 5.1, but the formal and measured net charge of both proteins differ by approximately 7u nits at pH 8.4. [4] The systematic absence of experimentally determinedv alues of Z has likely impeded ar igorous understanding of most chemicalp rocesses in which proteinsa re involved including aggregation and self-assembly, [20][21][22][23][24][25][26] ligand binding, [27][28][29][30][31][32][33][34] catalysis, [35][36][37][38][39] electron transfer, [3,6,[40][41][42][43][44][45][46][47] protein crystallization, [14,48] analytical separation, [49,50] and protein engineering. [51][52][53][54][55][56] It is tempting to assume that the formal net chargeo faprotein predicted from generalized residue pK a values (Z seq )issosimilar to the actual net charge that any difference is irrelevant, and the isoelectric point tells us all we need to know about ap rotein's net charge.…”

Phosphoryl‐Transfer Reaction in RNA under Alkaline Conditions

“…Thus, the solvent reaction field will be different for each solvent. Although the enzymatic environment is heterogeneous and much more complex than the model we use, the effect of the electric field on the mechanism and on the values of the free energies of activation allows us to obtain insight into the nature of the corresponding electric fields of enzymes and into the way enzymes catalyze the phosphoryl‐transfer reaction in RNA.…”

“…This theory was proposed in the context of an explicit formulation of the environment, but it can also be applied in an implicit model, such as the model used herein. It has been proposed that the inside of an enzyme can be modeled as a solvent with a value of the dielectric constant at around 4 when the enzyme is a protein or a molecule of RNA . For ϵ =4, our results indicate that the O2′‐P‐O5′ angle increases from 70° in R a to 120° in R r , with this last value still being quite far from linearity.…”