Negative Electrostatic Potential Regions Research Articles

Vibrational and structural observations and molecular docking study on 1-{3-(4-chlorophenyl)-5-[4-(propan-2-yl)phenyl]-4,5-dihydro-1H-pyrazol-1-yl}-ethanone

A combined experimental and theoretical analysis of on molecular structure, vibrational spectra and HOMO-LUMO analysis of 1-{3-(4-chlorophenyl)-5-[4-(propan-2-yl)phenyl]-4,5-dihydro-1H-pyrazol-1-yl}-ethanone is reported. The equilibrium geometry and vibrational wavenumbers have been computed using desnity functional B3LYP method with 6–311++G(d) (5D, 7F) as basis set. The nonlinear optical properties were evaluated by the determination of the first and second hyperpolarizabilities of the title compound. HOMO is localized over the whole molecule except the ring PhIII and the CH3 groups attached to the PhIII while the LUMO is located through out the whole molecule except the CH3 groups attached with the PhIII and this shows that an eventual charge transfer occurs within the molecule. From the molecular electrostatic potential study, the negative electrostatic potential regions are mainly localized over the carbonyl group, phenyl rings and are possible sites for electrophilic attack and the positive regions are localized over the nitrogen atoms as possible sites for nucleophilic attack. The docked ligand title compound forms a stable complex with kinesin spindle protein (KSP) and gives a binding affinity value of −6.7 kcal/mol the results suggest that the compound might exhibit inhibitory activity against KSP.

Structure and charge density distribution of amine azide based hypergolic propellant molecules: a theoretical study

A quantum chemical calculation and charge density analysis of some amine azide based propellants (DMAZ, DMAEH, ADMCPA, AMCBA and ACPA) have been carried out to understand the geometry, bond topological, electrostatic, and energetic properties. The topological properties of electron density of the molecules were determined using Bader’s theory of atoms in molecules from the wave functions obtained from the density functional method (B3LYP) with the 6-311G** basis set. The electron density distribution of these molecules reveals the nature of chemical bonding in the molecules. The azide group attached C−N bonds of all molecules exhibit the electron density of ρbcp(r) ∼1.639 e Å−3 and the Laplacian of electron density ∇2ρbcp(r) is ∼–14.0 e Å−5, in which the corresponding values of the ADMCPA molecule are relatively high, 1.725 e Å–3 and –15.2 e Å−5 respectively, whereas for the methylamine group attached C–N bonds, these values are found to be higher (1.824 e Å–3 and –17.25 e Å−5). The Laplacian of terminal N–N bonds of the azide group is highly negative, indicating that these charges are highly concentrated, whereas the charge concentration of the dimethylamine group attached N–N bond of DMEAH is very much less, confirming that the bond is the weakest bond among the molecules. The energy density has been calculated for each bond of the molecules, which insights the energy density distribution of the molecules. Relatively, the molecules exhibit distinct electrostatic properties that are related to different charge distribution in the molecules. Large negative electrostatic potential regions are found at the vicinity of the amine and azide groups of the molecules. The charge imbalance parameter of the molecules has been determined and shows that the DMAEH molecule is the least sensitive molecule in this series.

Spectroscopic investigation (FT-IR and FT-Raman), vibrational assignments, HOMO–LUMO analysis and molecular docking study of 1-hydroxy-4,5,8-tris(4-methoxyphenyl) anthraquinone

FT-IR and FT-Raman spectra of 1-hydroxy-4,5,8-tris(4-methoxyphenyl)anthraquinone were recorded and analyzed. The vibrational wavenumbers were computed using DFT quantum chemical calculations. The data obtained from wavenumber calculations were used to assign the vibrational bands obtained experimentally. A detailed molecular picture of the title compound and its interactions were obtained from NBO analysis. From the MEP plot it is clear that the negative electrostatic potential regions are mainly localized over carbonyl group. There is some evidence of a region of negative electrostatic potential due to π-electron density of the benzo groups. Molecular docking study shows that methoxy groups attached to the phenyl rings and hydroxyl group are crucial for binding and the title compound might exhibit inhibitory activity against PI3K and may act as an anti-neoplastic agent.

Molecular conformational analysis, vibrational spectra, NBO, NLO, HOMO–LUMO and molecular docking studies of ethyl 3-(E)-(anthracen-9-yl)prop-2-enoate based on density functional theory calculations

FT-IR and FT-Raman spectra of ethyl 3-(E)-(anthracen-9-yl)prop-2-enoate were recorded and analyzed. The conformational behavior of the molecule was also investigated. The vibrational wavenumbers were calculated using DFT quantum chemical calculations. The data obtained from the wavenumber calculations were used to assign vibrational bands obtained experimentally. The geometrical parameters are in agreement with XRD data. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. The HOMO and LUMO analysis were used to determine the charge transfer within the molecule and quantum chemical parameters related to the title compound. From the MEP analysis, it is clear that the negative electrostatic potential regions are mainly localized over the carbonyl groups and anthracene ring and are possible sites for electrophilic attack and the positive regions are localized at all the hydrogen atoms as possible sites for nucleophilic attack. NLO and NMR studies are also reported. Molecular docking studies suggest that the title compound might exhibit inhibitory activity against IDE and may act as an insulysin inhibitor. Conformational analysis is also reported.

Vibrational spectra, HOMO, LUMO, NBO, MEP analysis and molecular docking study of 2,2-diphenyl-4-(piperidin-1-yl)butanamide

The Fourier-Transform Infrared and Fourier-Transform Raman spectra of 2,2-diphenyl-4-(piperidin-1-yl)butanamide were recorded in the region 4000–400cm−1 and 4000–0cm−1. The vibrational wavenumbers are computed using HF and DFT methods. The complete vibrational assignments were performed on the basis of potential energy distribution using GAR2PED program. The geometrical parameters of the title compound are in agreement with the XRD data. From the MEP study, the negative electrostatic potential regions are mainly localized of carbonyl group and are possible sites for electrophilic attack and the positive regions are localized all the rings, indicating possible sites for nucleophilic attack. Stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using natural bond orbital analysis. The calculated HOMO and LUMO energies also confirm that charge transfer occurs within the molecule. PASS analysis of the title compound predicts among other activities, antidyskinetic activity. Molecular docking results draw us to the conclusion that the compound might exhibit inhibitory activity against adenosine A2A and may act as antidyskinetic agent.

1-Alkyl-1-methylpiperazine-1,4-diium salts: Synthetic, acid–base, XRD-analytical, FT-IR, FT-Raman spectral and quantum chemical study

We report the preparation and results of vibrational spectral analysis, which were obtained using both FT-IR and FT-Raman spectroscopy, for three 1-alkyl-1-methylpiperazine-1,4-diium salts (AMPSs), where alkyl is benzyl 4a, n-octadecyl 4b, and methyl 4c, respectively. These were prepared by multistep synthesis from piperazine. The acid–base study of AMPSs was performed and corresponding acid–base constants were obtained. Single crystals of AMPSs suitable for XRD-analysis were obtained and analyzed. The complete vibrational assignments of wavenumbers were made on the basis of a potential energy distribution. The HOMO and LUMO analysis was used to determine the charge transfer within the molecules. The calculated first hyperpolarizabilities of AMPSs 4a–4c are 48.34, 57.77 and 123.41 times that of urea. As can be seen from the MEP plots, the negative electrostatic potential regions are mainly localized over the chlorine and oxygen atoms for compounds 4a and 4b and chlorine and iodine atoms of compound 4c, and are possible sites for electrophilic attack.

Infrared spectrum, structural and optical properties and molecular docking study of 3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde have been investigated experimentally and theoretically. The title compound was optimized using at HF and DFT levels of calculations. The B3LYP/6-311++G(d,p) (5D,7F) results and in agreement with experimental infrared bands. The normal modes are assigned using potential energy distribution. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using natural bonding orbital analysis. The frontier molecular orbital analysis is used to determine the charge transfer within the molecule. From molecular electrostatic potential map, it is evident that the negative electrostatic potential regions are mainly localized over the carbonyl group and mono substituted phenyl ring and are possible sites for electrophilic attack and, positive regions are localized around all para substituted phenyl and pyrazole ring, indicating possible sites for nucleophilic attack. First hyperpolarizability is calculated in order to find its role in nonlinear optics. The geometrical parameters are in agreement with experimental data. From the molecular docking studies, it is evident that the fluorine atom attached to phenyl ring and the carbonyl group attached to pyrazole ring are crucial for binding and the results draw us to the conclusion that the compound might exhibit phosphodiesterase inhibitory activity.

Spectroscopic investigation (FT-IR, FT-Raman), HOMO–LUMO, NBO analysis and molecular docking study of 2-[(4-chlorobenzyl)sulfanyl]-4-(2-methylpropyl)-6-[3-trifluoromethyl)-anilino]pyrimidine-5-carbonitrile, a potential chemotherapeutic agent

FT-IR and FT-Raman spectra of 2-[(4-chlorobenzyl)sulfanyl]-4-(2-methylpropyl)-6-[3-trifluoromethyl)-anilino]pyrimidine-5-carbonitrile were recorded and analyzed. The vibrational wave numbers were computed using DFT quantum chemical calculations. The data obtained from wave number calculations are used to assign vibrational bands obtained in infrared and Raman spectra. Potential energy distribution was done using GAR2PED program. The NH stretching wave number is red shifted by102cm−1 in IR from the computed wave number, which indicates the weakening of the NH bond. The geometrical parameters (DFT) of the title compound are in agreement with the XRD results. NBO analysis, HOMO–LUMO, first hyperpolarizability and molecular electrostatic potential results are also reported. From the MEP map it is evident that the negative electrostatic potential regions are mainly localized over the CN and CF3 groups and are possible sites for electrophilic attack and positive regions are localized around NH group, indicating possible sites for nucleophilic attack. The preliminary docking results suggest that the title compound might exhibit inhibitory activity against GPb and may act as a potential anti-diabetic compound.

Ab initio crystal structure and charge density distribution of a highly energetic 2,4-dinitrobenzoic acid molecule

The energetic parameters, such as density, bond strength, and sensitivity of explosives/ propellants decide their detonation power and safety. Experimentally, optimization of these parameters is found to be a difficult task; therefore, prior to synthesis, it makes sense to estimate these parameters by computational techniques, ab initio crystal structure prediction, and quantum chemical calculation coupled with the AIM analysis. Here, we predict the density of an energetic 2,4-dinitrobenzoic acid (DNBA) molecule from different ab initio crystal structure models and validate the results through comparisons with experimental data. The bond topological characterization reveals that the C NO2 bonds are the weakest bonds and are identified as sensitive bonds in the molecule. The bond sensitivity is estimated from Murray’s method. The impact sensitivity of this molecule is also calculated. Large negative electrostatic potential regions are found near the NO2 and carboxylic groups, which are the reactive sites of the molecule.

Electronic memory devices based on the chalcone with negative electrostatic potential regions

The molecular electrostatic potential (ESP) properties were used for the explanation of organic electric memory ability. Several chalcone compounds, owning a negative ESP region locates at the oxygen atom, were selected in this paper to validate the selection of compounds for organic memory materials. The synthesis, characterization, fabrication of the organic memory devices and the electrical properties for them were reported, and they were shown as WORM (write once read many times) type memory devices. The molecular geometries were optimized by the addition of a changeable electric field in the x direction inside the molecules using FF-DFT (Finite Field-Density Functionary Theory) method. The relationship between ESP of the molecules under different electric field and the property was discussed, and the mechanisms associated with the memory effect were also elucidated from DFT calculation results.

Charge density distribution and the electrostatic moments of CTPB in the active site of p300 enzyme: A DFT and charge density study

A molecular docking and charge density analysis have been carried out to understand the conformational change, charge distribution and electrostatic properties of N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide (CTPB) in the active site of p300. The nearest neighbors, shortest intermolecular contacts between CTPB-p300 and the lowest binding energy of CTPB have been analyzed from the docking analysis. Further, a charge density analysis has been carried out for the molecule in gas phase and for the corresponding molecule lifted from the active site of p300. Due to the intermolecular interaction between CTPB and the amino acids of active site, the conformation of the CTPB has been significantly altered (particularly the pentadecyl chain). CTPB forms strong interaction with the amino acid residues Tyr1397 and Trp1436 at the distance 2.12 and 2.72Å, respectively. However, the long pentadecyl alkyl chain of CTPB produces a barrier and reducing the chance of forming hydrogen bonding with p300. The electron density ρbcp(r) of the polar bonds (C–O, C–N, C–F and C–Cl) of CTPB are increased when it present in the active site. The dipole moment of CTPB in the active site is significantly less (5.73D) when compared with the gas phase (8.16D) form. In the gas phase structure, a large region of negative electrostatic potential (ESP) is found at the vicinity of O(2) and CF3 group, which is less around the O(1) atom. Whereas, in the active site, the negative ESP around the CF3 group is decreased and increased at the O(1) and O(2)-atoms. The ESP modifications of CTPB in the active site are mainly attributed to the effect of intermolecular interaction. The gas phase and active site study insights the molecular flexibility and the electrostatic properties of CTPB in the active site.

Rattling Motion of Alkali Metal Ions through the Cavities of Model Compounds of Graphyne and Graphdiyne

We study the passage of the alkali metal ions (Li(+), Na(+), and K(+)) through some conjugated carbon-based ring systems, starting from C12H6 and C24H12 (tribenzocyclyne; TBC), which serve as model compounds for graphyne to some of the higher analogues, C26H12, C28H12, and C30H12, the model systems for graphdiyne. The motion of the ions through cyclic carbon clusters, C12 and C14, is also investigated. The potential for the motion of the ions from one side of the ring to the other through the cavities of the molecules is a symmetric double well in most cases, while it is a rather flat potential in others, arising due to the free motion of the ions through the cavities. Electrostatic potential (ESP) analyses reveal that the ions bind to the ring systems at the most negative regions of ESP. The estimated energy barriers for the motion of Li(+) through C12H6 and C24H12 are 4.7 and 4.3 kcal mol(-1), respectively, and are comparable to the barrier for the classic case of umbrella-like inversion in ammonia. Transmission of Li(+) through C26H12, C28H12, C30H12, C12, and C14 rings is barrierless. We predict that the rattling motion of Li(+) through the model compounds of graphyne and graphdiyne should be experimentally observable. We also model the effectively one-dimensional motion of the ions through the rings using discrete variable representation (DVR) and calculate the energy levels of the complexes in the symmetric double well potentials. The molecular orbital analyses and the nuclear independent chemical shift (NICS) values for the rings suggest distinct trends based on the (4n + 2/4n) π electron count, leading us to propose two neutral complexes, (C12H6)Li2 and (C24H12)Li2, that are highly stable with binding energies of 400 and 356 kcal mol(-1), respectively.

The Cation−π Interaction

The chemistry community now recognizes the cation-π interaction as a major force for molecular recognition, joining the hydrophobic effect, the hydrogen bond, and the ion pair in determining macromolecular structure and drug-receptor interactions. This Account provides the author's perspective on the intellectual origins and fundamental nature of the cation-π interaction. Early studies on cyclophanes established that water-soluble, cationic molecules would forego aqueous solvation to enter a hydrophobic cavity if that cavity was lined with π systems. Important gas phase studies established the fundamental nature of the cation-π interaction. The strength of the cation-π interaction (Li(+) binds to benzene with 38 kcal/mol of binding energy; NH4(+) with 19 kcal/mol) distinguishes it from the weaker polar-π interactions observed in the benzene dimer or water-benzene complexes. In addition to the substantial intrinsic strength of the cation-π interaction in gas phase studies, the cation-π interaction remains energetically significant in aqueous media and under biological conditions. Many studies have shown that cation-π interactions can enhance binding energies by 2-5 kcal/mol, making them competitive with hydrogen bonds and ion pairs in drug-receptor and protein-protein interactions. As with other noncovalent interactions involving aromatic systems, the cation-π interaction includes a substantial electrostatic component. The six (four) C(δ-)-H(δ+) bond dipoles of a molecule like benzene (ethylene) combine to produce a region of negative electrostatic potential on the face of the π system. Simple electrostatics facilitate a natural attraction of cations to the surface. The trend for (gas phase) binding energies is Li(+) > Na(+) > K(+) > Rb(+): as the ion gets larger the charge is dispersed over a larger sphere and binding interactions weaken, a classical electrostatic effect. On other hand, polarizability does not define these interactions. Cyclohexane is more polarizable than benzene but a decidedly poorer cation binder. Many studies have documented cation-π interactions in protein structures, where lysine or arginine side chains interact with phenylalanine, tyrosine, or tryptophan. In addition, countless studies have established the importance of the cation-π interaction in a range of biological processes. Our work has focused on molecular neurobiology, and we have shown that neurotransmitters generally use a cation-π interaction to bind to their receptors. We have also shown that many drug-receptor interactions involve cation-π interactions. A cation-π interaction plays a critical role in the binding of nicotine to ACh receptors in the brain, an especially significant case. Other researchers have established important cation-π interactions in the recognition of the "histone code," in terpene biosynthesis, in chemical catalysis, and in many other systems.

Structure-Activity Relationship Studies of a Number of α1 -Adrenoceptor Antagonists and Antiarrhythmic Agents.

Arylpiperazines represent one of the most studied classes of α1 -adrenoceptor (α1 -AR) antagonists. Currently, α1 -AR antagonists are useful in the treatment of benign prostatic hyperplasia, lower urinary tract symptoms or cardiac arrhythmia. The activity of various derivatives of 1-[3-(4-arylpiperazin-1-yl)propyl]pyrrolidin-2-one as α1 -adrenergic receptor antagonists and antiarrhythmic (AA) agents was described using the qualitative inverse Structure Activity Relationship (SAR) model. The three-dimensional structures of the pyrrolidin-2-one derivatives in the basic form were obtained using AM1 semi-empirical quantum chemical calculations. All the molecules were geometry-optimized until the root-mean-square (RMS) gradient value was smaller than 10(-6) a.u. Single-point energy (SPE) calculations were performed at the DFT/B3LYP level of theory using the 6-31G** basis set. The main focus of this inverse SAR study is to find which features cause enhancing of antiarrhythmic properties between subtly different types of activity (α1 -adrenoreceptor antagonists and antiarrhythmic activities). Our SAR study involves the charge distribution in the plane of the pharmacophore model for α1 -AR. Suitable maps of the electrostatic potential were plotted based on the electronic and nuclear charge distribution obtained from the energy calculations. The results of this modelling study indicate that if the terminal arylpiperazine moiety is surrounded by regions of negative electrostatic potential, then the antiarrhythmic activity is blocked.

Protein Selectivity Factors as a Molecular Basis for Metal Toxicity

Toxic metals are known to displace physiologically-relevant metal ions in proteins, and may activate or deactivate protein function in response to changes in the free metal concentration. To investigate potential relationships between metal/protein complexes and toxicity, an analysis of proteins structural and sequential data was used to establish statistical bases for identifying key selectivity factors associated with Pb2+-protein binding. These data led us to hypothesize that Pb2+, and potentially other toxic metals, may induce opportunistic binding in regions of negative electrostatic potential, thus altering the proteins conformation.To compare structural/conformational changes, investigate selectivity and affinity, and probe the mechanism of toxic metal-protein interactions, several natural and engineered Ca2+-binding proteins (CaBPs) were analyzed using Fluorescence, CD and 1D and 2D NMR spectroscopy. Engineered proteins were developed based on grafting methods that involved insertion of metal-binding motifs in flexible regions of protein scaffolds to investigate biophysical properties associated with binding reactions in isolated sites. Additionally, the ubiquitous signaling protein calmodulin (CaM) was evaluated extensively to determine changes associated with competitive binding between Ca2+ and anthropogenically available toxicants such as Pb2+, Gd3+, La3+, Tb3+ and In3+. Results suggest that certain toxic metals may not only displace the biologically-relevant metals in metalloproteins, but support our hypothesis that opportunistic binding occurs in non-sites. This has important implications for the potential binding of toxic metals by non-metalloproteins, as well as providing a basis for understanding the impact of toxicity related to downstream protein-protein interactions.

Comparison of properties of particles of Cucumber mosaic virus and Tomato aspermy virus based on the analysis of molecular surfaces of capsids

The plant RNA viruses Cucumber mosaic virus (CMV) and Tomato aspermy virus (TAV) (genus Cucumovirus) have similar icosahedral particles, the crystal structures of which have been reported recently. Similarity in particle structure agrees with reports of stable capsids assembled from their capsid proteins and of viable recombinant viruses with chimeric capsid proteins derived from CMV and TAV. However, differences between the cucumoviruses have been reported for physicochemical properties. Here, structural and electrostatic features of the molecular surfaces are studied to investigate their relationship with these observations. Two coat-protein recombinants with structures modelled by taking CMV and TAV as templates were also included in the analysis. Results show that there exists an external region of negative electrostatic potential that has arisen from strictly conserved charged residues situated near the external HI loop of the subunits in the capsomers. This negative domain surrounds the fivefold and quasi-sixfold axes and locates above regions of positive potential that extend to cover, nearly homogeneously, the inner surface of capsids, where interaction with encapsidated RNA occurs. Differences between the outer electrostatic distributions in CMV and TAV explain the distinct response of both viruses to variations in physicochemical conditions required for particle stability and are essential to rationalize the biological activity of the coat-protein recombinants, in spite of their seemingly distinct electrostatic characteristics.

ANALYSIS OF MOLECULAR STEREOELECTRONIC SIMILARITY BETWEEN N,N-DIETHYL-M-TOLUAMIDE (DEET) ANALOGS AND INSECT JUVENILE HORMONE TO DEVELOP A MODEL PHARMACOPHORE FOR INSECT REPELLENT ACTIVITY

Similarity analysis on molecular stereoelectronic properties of N,N-diethyl-m-toluamide (DEET), natural insect juvenile hormone (JH), a synthetic insect juvenile hormone mimic (JH-mimic, undecen-2-yl carbamate), and DEET compounds reveals remarkable similarities that lead to a reliable pharmacophore for the design of efficacious insect repellents and provide insights for understanding the mechanism of repellent action. The study involves an AM1 quantum chemical computational procedure enabling a conformational search for the lowest and most abundant energy conformers of JH, JH-mimic, and 15 DEET compounds and complete geometry optimization of the conformers. Similarity analyses of stereoelectronic properties such as structural parameters, atomic charges, dipole moments, molecular electrostatic potentials, and highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies were performed on JH, JH-mimic, and the DEET compounds. Similarity of stereoelectronic attributes of the amide/ester moiety, negative electrostatic potential regions beyond the molecular surface, and a large distribution of hydrophobic regions in the compounds appears to be the 3 important factors leading to a similar interaction with the JH receptor. The similarity of electrostatic profiles beyond the molecular surface is likely to play a crucial role toward molecular recognition interaction with the JH receptor from a distance which suggests a possible electrostatic bioisosterism of the amide group of the DEET compounds and JH-mimic and, thus, a model for molecular recognition at the JH receptor.

A thermodynamic framework for Mg2+ binding to RNA.

We present a model describing how Mg(2+) binds and stabilizes specific RNA structures. In this model, RNA stabilization arises from two energetically distinct modes of Mg(2+) binding: diffuse- and site-binding. Diffusely bound Mg(2+) are electrostatically attracted to the strong anionic field around the RNA and are accurately described by the Poisson-Boltzmann equation as an ensemble distributed according to the electrostatic potentials around the nucleic acid. Site-bound Mg(2+) are strongly attracted to specifically arranged electronegative ligands that desolvate the ion and the RNA binding site. Thus, site-binding is a competition between the strong coulombic attraction and the large cost of desolvating the ion and its binding pocket. By using this framework, we analyze three systems where a single site-bound Mg(2+) may be important for stability: the P5 helix and the P5b stem loop from the P4-P6 domain of the Tetrahymena thermophila group I intron and a 58-nt fragment of the Escherichia coli 23S ribosomal RNA. Diffusely bound Mg(2+) play a dominant role in stabilizing these RNA structures. These ions stabilize the folded structures, in part, by accumulating in regions of high negative electrostatic potential. These regions of Mg(2+) localization correspond to ions that are observed in the x-ray crystallographic and NMR structures of the RNA. In contrast, the contribution of site-binding to RNA stability is often quite small because of the large desolvation penalty. However, in special cases, site-binding of partially dehydrated Mg(2+) to locations with extraordinarily high electrostatic potential can also help stabilize folded RNA structures.

Crystal structure of outer surface protein C (OspC) from the Lyme disease spirochete, Borrelia burgdorferi.

Outer surface protein C (OspC) is a major antigen on the surface of the Lyme disease spirochete, Borrelia burgdorferi, when it is being transmitted to humans. Crystal structures of OspC have been determined for strains HB19 and B31 to 1.8 and 2.5 A resolution, respectively. The three-dimensional structure is predominantly helical. This is in contrast to the structure of OspA, a major surface protein mainly present when spirochetes are residing in the midgut of unfed ticks, which is mostly beta-sheet. The surface of OspC that would project away from the spirochete's membrane has a region of strong negative electrostatic potential which may be involved in binding to positively charged host ligands. This feature is present only on OspCs from strains known to cause invasive human disease.

Mg2+ binding to tRNA revisited: the nonlinear poisson-boltzmann model

Our current understanding of Mg2+ binding to RNA, in both thermodynamic and structural terms, is largely based on classical studies of transfer RNAs. Based on these studies, it is clear that magnesium ions are crucial for stabilizing the folded structure of tRNA. We present here a rigorous theoretical model based on the nonlinear Poisson-Boltzmann (NLPB) equation for understanding Mg2+ binding to yeast tRNAPhe. We use this model to interpret a variety of experimental Mg2+ binding data. In particular, we find that the NLPB equation provides a remarkably accurate description of both the overall stoichiometry and the free energy of Mg2+ binding to yeast tRNAPhe without any fitted parameters. In addition, the model accurately describes the interaction of Mg2+ with localized regions of the RNA as determined by the p Ka shift of differently bound fluorophores. In each case, we find that the model also reproduces the univalent salt-dependence and the anticooperativity of Mg2+ binding. Our results lead us to a thermodynamic description of Mg2+ binding to yeast tRNAPhe based on the NLPB equation. In this model, Mg2+ binding is simply explained by an ensemble of ions distributed according to a Boltzmann weighted average of the mean electrostatic potential around the RNA. It appears that the entire ensemble of electrostatically bound ions superficially mimics a few strongly coordinated ions. In this regard, we find that Mg2+ stabilizes the tertiary structure of yeast tRNAPhe in part by accumulating in regions of high negative electrostatic potential. These regions of Mg2+ localization correspond to bound ions that are observed in the X-ray crystallographic structures of yeast tRNAPhe. Based on our results and the available thermodynamic data, there is no evidence that specifically coordinated Mg ions have a significant role in stabilizing the native tertiary structure of yeast tRNAPhe in solution.