Geometric characteristics and energy landscapes of halogen–water–hydrogen bridges at protein–ligand interfaces

Lu, Shaoyong; Jiang, Yong‐Jun; Zhou, Peng; Zou, Jian‐Wei; Wu, Tingfeng

doi:10.1016/j.cplett.2009.12.077

Cited by 11 publications

(6 citation statements)

References 34 publications

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“…The AIM results revealed that the values of ρ b were calculated to be 0.0267 au and 0.0201 au for the valmerin-19 in GSK3β and CDK5, respectively. These values, given at the HBCPs, are within the accepted values for the formation of the hydrogen bonding interactions [22,43], suggesting that the intramolecular weak H bond exists in the valmerin-19. The formation of this intramolecular H bond rendered the urea group of the valmerin-19 orient the hinge residues of GSK3β/CDK5.…”

Section: Inhibitor-residue Interaction Decompositionsupporting

confidence: 55%

“…Dramatically, an intramolecular weak H bond connecting the second NH of urea with the nitrogen pyridine atom (N-H•••N) was formed for the valmerin-19 in both systems. The existence of the intramolecular H bond in the valmerin-19 was further validated using the AIM method, which has been successfully applied to study properties of a variety of conventional and unconventional H bonds [22,43]. The properties at the hydrogen bond critical points (HBCPs), in principle, were analyzed using the following parameter: the value of charge density (ρ b ).…”

Section: Inhibitor-residue Interaction Decompositionmentioning

confidence: 99%

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Structural basis of valmerins as dual inhibitors of GSK3β/CDK5

Wang

Tian

et al. 2014

J Mol Model

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Development of multi-target drugs is becoming increasingly attractive in the repertoire of protein kinase inhibitors discovery. In this study, we carried out molecular docking, molecular dynamics simulations, molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations, principal component analysis (PCA), and dynamical cross-correlation matrices (DCCM) to dissect the molecular mechanism for the valmerin-19 acting as a dual inhibitor for glycogen synthase kinase 3β (GSK3β) and cyclin-dependent kinase 5 (CDK5). Detailed MM-PBSA calculations revealed that the binding free energies of the valmerin-19 to GSK3β/CDK5 were calculated to be -12.60 ± 2.28 kcal mol(-1) and -11.85 ± 2.54 kcal mol(-1), respectively, indicating that valmerin-19 has the potential to act as a dual inhibitor of GSK3β/CDK5. The analyses of PCA and DCCM results unraveled that binding of the valmerin-19 reduced the conformational dynamics of GSK3β/CDK5 and the valmerin-19 bound to GSK3β/CDK5 might occur mostly through a conformational selection mechanism. This study may be helpful for the future design of novel and potent dual GSK3β/CDK5 inhibitors.

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Section: Inhibitor-residue Interaction Decompositionsupporting

confidence: 55%

Section: Inhibitor-residue Interaction Decompositionmentioning

confidence: 99%

Structural basis of valmerins as dual inhibitors of GSK3β/CDK5

Wang

Tian

et al. 2014

J Mol Model

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“…This is borne out by the negative surface potential of most electrolyte solutions (29), by surfacespecific spectroscopic studies (30)(31)(32)(33), and by theoretical predictions. The adsorption of ions to the surface was surmised long ago from the surface tension minima observed in electrolyte solutions at approximately 1 mM.…”

Section: Fig 1 Displays Mass Spectral Nomentioning

confidence: 99%

Anions dramatically enhance proton transfer through aqueous interfaces

Mishra

Enami

Nielsen

et al. 2012

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

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Proton transfer (PT) through and across aqueous interfaces is a fundamental process in chemistry and biology. Notwithstanding its importance, it is not generally realized that interfacial PT is quite different from conventional PT in bulk water. Here we show that, in contrast with the behavior of strong nitric acid in aqueous solution, gas-phase HNO 3 does not dissociate upon collision with the surface of water unless a few ions (>1 per 10 6 H 2 O) are present. By applying online electrospray ionization mass spectrometry to monitor in situ the surface of aqueous jets exposed to HNO 3ðgÞ beams we found that NO 3 − production increases dramatically on >30-μM inert electrolyte solutions. We also performed quantum mechanical calculations confirming that the sizable barrier hindering HNO 3 dissociation on the surface of small water clusters is drastically lowered in the presence of anions. Anions electrostatically assist in drawing the proton away from NO 3 − lingering outside the cluster, whose incorporation is hampered by the energetic cost of opening a cavity therein. Present results provide both direct experimental evidence and mechanistic insights on the counterintuitive slowness of PT at water-hydrophobe boundaries and its remarkable sensitivity to electrostatic effects.air-water interface | acid-base | catalysis | nitric acid dissociation P roton transfers (PTs) at water interfaces, such as water boundaries with air (1, 2) or lipid membranes (3), intervene in fundamental phenomena. Arguably the most important PTs are those that take place through and across water boundaries rather than in the bulk liquid. Interfacial PTs participate in the acidification of the ocean (4), the chemistry of atmospheric gases and aerosols (1,5,6), the generation of the electrochemical gradients that drive energy transduction across biomembranes (3,7,8), and in enzymatic function (9, 10) because the activation of neutral species is most generally accomplished via acid-base catalysis (11). Interfacial PT, in contrast with conventional PT in bulk water, depends sensitively on the extent of ion hydration because the density of water in interfacial layers vanishes within 1-nm (12). The acidity of hydronium at the interface, H 3 O þ ðifÞ , is therefore expected to bridge that of H 3 O þ ðgÞ , which protonates most nonalkane species in the gas-phase (13), and H 3 O þ ðaqÞ , which neutralizes only relatively strong bases in solution. Critically controlled by ion hydration in thin yet cohesive interfacial water layers that resist ion penetration, PT "on water" clearly confronts unique constraints. Species that behave as strong acids "in water" may become weak ones on water if dissociation were hindered by kinetic and/or thermodynamic factors in the interfacial region (14, 15).Herein we address these important issues and report the results of experiments in which we monitor the dissociation of gaseous nitric acid HNO 3ðgÞ molecules in collisions with interfacial water, H 2 O ðifÞ , reaction 1 (Eq. 1):[1]The Technique Experiments were conduc...

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“…Since the theory behind the various DFT functionals was clarified fairly well in the original literature, we herein refer the readers to these references for those details. Except two more recent DFT methods, M06 and M06-HF, these others tested density functionals that selected here for evaluation were based on at least one of the following reasons: (i) has been used to study the nonbonding interactions in biomolecule systems [25,27,31,52,55,63,64]; (ii) has been used to investigate the bondings involving halogens or halides [65][66][67][68][69], such as halogenwater-hydrogen bridges [70], halogen bondings [71], fluorine bondings [24]; (iii) has been used to determine the intermolecular interaction potentials [72]; (iv) has been used to study the hydrogen bonding systems [73][74][75][76][77]; (v) has been used to predict the binding energies of some dispersion-bound complexes [78].…”

Section: Quantum-mechanical (Qm) Calculationsmentioning

confidence: 99%

A systematical comparison of DFT methods in reproducing the interaction energies of halide series with protein moieties

2011

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A systematic theoretical investigation on the interaction energies of halogen-ionic bridges formed between halide ions and the polar H atoms bonded to N of protein moieties has been carried out by employing a variety of density functional methods. In this procedure, full geometry optimizations are performed at the Møller-Plesset second-order perturbation (MP2) level of theory in conjunction with the Dunning's augmented correlation-consistent basis set, aug-cc-pVDZ. Subsequently, two distinct basis sets, i.e. 6-311++G(df,pd) and aug-cc-pVTZ, are employed in the following single-point calculations so as to check the stability of the results obtained at the different levels of DFT. The performance of DFT methods has been evaluated by comparing the results with those obtained from the rigorous MP2 theory. It is shown that the B98, B97-1, and M05 give the lowest root-mean-square error (RMSE) for predicting fluoride-binding energies, M05-2X, MPW1B95, and MPW1PW91 have the best performance in reproducing chloride-binding energies, B97-1, PBEKCIS, and PBE1KCIS present the optimal result for bromide-binding energies, while B97-1, MPW1PW91, and TPSS perform most well on iodide-binding energies. The popular B3LYP functional seems to be quite modest for studying halide-protein moiety interactions. In addition, the PBE1KCIS functional provide accuracies close to the computationally expensive MP2 method for the calculation of interaction energies of all halide-binding systems.

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Geometric characteristics and energy landscapes of halogen–water–hydrogen bridges at protein–ligand interfaces

Cited by 11 publications

References 34 publications

Structural basis of valmerins as dual inhibitors of GSK3β/CDK5

Structural basis of valmerins as dual inhibitors of GSK3β/CDK5

Anions dramatically enhance proton transfer through aqueous interfaces

A systematical comparison of DFT methods in reproducing the interaction energies of halide series with protein moieties

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