Close-Range Electrostatic Interactions in Proteins

Kumar, Sandeep; Nussinov, Ruth

doi:10.1002/1439-7633(20020703)3:7<604::aid-cbic604>3.0.co;2-x

Cited by 503 publications

(427 citation statements)

References 33 publications

Supporting

Mentioning

399

Contrasting

Order By: Relevance

“…Although the van der Waals' interactions are crucial toward attaining the functional structure of the protein, the allosteric modulation due to ligand binding seems to be strongly associated with the electrostatic interactions. Our findings provide further support to the already established view regarding the significant role of electrostatic interactions in biomolecular functions including allostery (38,(44)(45)(46)(47)(48).…”

Section: Resultssupporting

confidence: 89%

Hidden electrostatic basis of dynamic allostery in a PDZ domain

Kumawat

Chakrabarty

2017

Proc. Natl. Acad. Sci. U.S.A.

138

View full text Add to dashboard Cite

Allosteric effect implies ligand binding at one site leading to structural and/or dynamical changes at a distant site. PDZ domains are classic examples of dynamic allostery without conformational changes, where distal side-chain dynamics is modulated on ligand binding and the origin has been attributed to entropic effects. In this work, we unearth the energetic basis of the observed dynamic allostery in a PDZ3 domain protein using molecular dynamics simulations. We demonstrate that electrostatic interaction provides a highly sensitive yardstick to probe the allosteric modulation in contrast to the traditionally used structure-based parameters. There is a significant population shift in the hydrogen-bonded network and salt bridges involving side chains on ligand binding. The ligand creates a local energetic perturbation that propagates in the form of dominolike changes in interresidue interaction pattern. There are significant changes in the nature of specific interactions (nonpolar/ polar) between interresidue contacts and accompanied side-chain reorientations that drive the major redistribution of energy. Interestingly, this internal redistribution and rewiring of side-chain interactions led to large cancellations resulting in small change in the overall enthalpy of the protein, thus making it difficult to detect experimentally. In contrast to the prevailing focus on the entropic or dynamic effects, we show that the internal redistribution and population shift in specific electrostatic interactions drive the allosteric modulation in the PDZ3 domain protein.A llosteric regulation of proteins plays a key role in physiological cell functions, biochemical and signal transduction pathways, and drug discovery (1-3). It has remained a challenge to understand how the thermodynamic perturbation caused by ligand binding at one site would propagate and modulate the structure and dynamics of distal regions of proteins. The prevailing models of structure-based allostery (4, 5) do not apply to the more recent examples of allostery without conformational change such as PDZ domain (6), CAP dimer (7), and met repressor (8). These examples have triggered the concept of dynamic allostery, where the side-chain dynamics is modulated on ligand binding and the origin has often been attributed to changes in the conformational entropy (9, 10). The modern view of allostery invokes a thermodynamic picture, where a population shift among preexisting conformational states occurs on binding the allosteric effector (11-13). It has also been suggested in the context of allostery without conformational change that "not observed does not imply that it is not there" (10) because crystallographic techniques may not resolve the relatively minor population shifts. An interesting idea has emerged that all proteins might be allosteric in nature (14).PDZ domain has been a classic model system to study single domain allostery without major structural changes (9, 15, 16) (Fig. 1A). PDZ domains are evolutionary conserved proteinprotein interaction module...

show abstract

Section: Resultssupporting

confidence: 89%

Hidden electrostatic basis of dynamic allostery in a PDZ domain

Kumawat

Chakrabarty

2017

Proc. Natl. Acad. Sci. U.S.A.

138

View full text Add to dashboard Cite

show abstract

“…238 The latter might in turn stem from charge patchiness and propensity of HB formation between the residues along the contact surface of the bound proteins. 279,280 Several issues offer a perspective for future studies. First, for evaluation of ES binding energies for DNA-protein complexes, on top of the statistical analysis of charge patterns described above, one needs to guess 281,282 a rather small dielectric constant e c in the space between DNA and protein.…”

Section: Approximations and Perspectivesmentioning

confidence: 99%

Electrostatic interactions in biological DNA-related systems

Cherstvy

2011

Phys. Chem. Chem. Phys.

162

148

View full text Add to dashboard Cite

In this perspective article, we focus on recent developments in the theory of charge effects in biological DNA-related systems. The electrostatic effects on different levels of DNA organization are considered, including the DNA-DNA interactions, DNA complexation with cationic lipid membranes, DNA condensates and DNA-dense cholesteric phases, protein-DNA recognition, DNA wrapping in nucleosomes, and inter-nucleosomal interactions. For these systems, we develop a theoretical framework to describe the physical-chemical mechanisms of structure formation and anticipate some biological consequences. General biophysical principles of DNA compaction in chromatin fibers and DNA spooling inside viral capsids are discussed in the end, with emphasis on electrostatic aspects.

show abstract

“…DOI: 10.1103/PhysRevLett.109.257802 PACS numbers: 77.84.Nh, 31.15.xr, 31.70.Dk, 78.20.Ci Salt ions are essential in biology, colloidal science, electrochemistry, and many other areas of science and engineering. For example, protein stability and solubility are well known to be significantly affected by the addition of salts [1]. In the energy arena, there is much current interest in lithium salt-doped polymers as new battery materials [2].…”

mentioning

confidence: 99%

“…For example, protein stability and solubility are well known to be significantly affected by the addition of salts [1]. In the energy arena, there is much current interest in lithium salt-doped polymers as new battery materials [2].…”

mentioning

confidence: 99%

Ion Solvation in Liquid Mixtures: Effects of Solvent Reorganization

2012

View full text Add to dashboard Cite

Using field-theoretic techniques, we study the solvation of salt ions in liquid mixtures, accounting for the permanent and induced dipole moments, as well as the molecular volume of the species. With no adjustable parameters, we predict solvation energies in both single-component liquids and binary liquid mixtures that are in excellent agreement with experimental data. Our study shows that the solvation energy of an ion is largely determined by the local response of the permanent and induced dipoles, as well as the local solvent composition in the case of mixtures, and does not simply correlate with the bulk dielectric constant. In particular, we show that, in a binary mixture, it is possible for the component with the lower bulk dielectric constant but larger molecular polarizability to be enriched near the ion. DOI: 10.1103/PhysRevLett.109.257802 PACS numbers: 77.84.Nh, 31.15.xr, 31.70.Dk, 78.20.Ci Salt ions are essential in biology, colloidal science, electrochemistry, and many other areas of science and engineering. For example, protein stability and solubility are well known to be significantly affected by the addition of salts [1]. In the energy arena, there is much current interest in lithium salt-doped polymers as new battery materials [2].The effects of salt ions on the properties of soft matter can often be understood in terms of translational entropy and electrostatic screening. However, recently it has been shown that the solvation energy of the salt ions can significantly affect the phase behavior [3,4] and interfacial properties of liquid mixtures [5][6][7][8]. For example, Ref. [4] showed that the dramatic increase in the order-disorder transition temperature of (polyethylene oxide)-b-polystyrene block copolymers upon adding a small amount of lithium salt can be explained on the basis of the preferential solvation energy of the anions. Physically, the tendency of an ion to be preferentially solvated by the more polarizable component in a two-component mixture provides a significant driving force for phase separation [3], as well as differential adsorption between the cation and anion at the interface [5][6][7][8].While a very large body of theoretical literature exists for ion solvation in single-component liquids for comprehensive reviews and Ref. [14] for recent developments of ion force fields for solvation.), we are not aware of any theory that predicts the composition dependence of ion solvation in liquid mixtures. In Refs. [3][4][5][6]8], the solvation energy is modeled phenomenologically at the linear dielectrics level by a crude Born expression: ÁG Born ¼ ½ðzeÞ 2 =ð8 a 0 Þ ð1=" À 1Þ, where e is the elementary charge, a is the radius of the ion, and z is the valency. The local dielectric constant is taken to be given by a simple composition weighted average " ¼ " A A þ " B B . The Born model has the virtue of being simple and intuitive in capturing the essential qualitative physics of solvation. However, quantitatively, the Born expression is known to be a poor description of the solva...

show abstract

Close-Range Electrostatic Interactions in Proteins

Cited by 503 publications

References 33 publications

Hidden electrostatic basis of dynamic allostery in a PDZ domain

Hidden electrostatic basis of dynamic allostery in a PDZ domain

Electrostatic interactions in biological DNA-related systems

Ion Solvation in Liquid Mixtures: Effects of Solvent Reorganization

Contact Info

Product

Resources

About