Biomedical subjects

Kwang S Kim

Publications and source records attributed to Kwang S Kim.

63 records · Page 4Linked to original sources

PubMed2003

Molecular recognition of fluoride anion: benzene-based tripodal imidazolium receptor.

A benzene-based tripodal imidazolium receptor utilizing the strong (C-H)(+)...X(-) hydrogen bonding interaction between imidazolium moieties and halide anions is extensively investigated both theoretically and experimentally. Ab initio calculations predict that this receptor has a very high affinity for fluoride ion (F(-)). The association constant and free energy gain of the N-butyl receptor 2 for F(-) in acetonitrile were measured to be 2.1 x 10(5) M(-1) and -7.25 kcal/mol, respectively, showing that the receptor has a high affinity for F(-) in highly polar organic solvents.

Journal Article↗

PubMed2003

Rational design of biologically important chemosensors: a novel receptor for selective recognition of acetylcholine over ammonium cations.

[structure: see text] In consideration of competition between cation-pi and hydrogen bond interaction forces, we designed a novel receptor, 1,3,5-tris(pyrrolyl)benzene, which shows high selectivity for acetylcholine (ACh). The selectivity of the receptor for ACh over other ammonium cations is demonstrated by the ion-selective electrode (ISE) method in buffer solution. The binding free energy of the receptor with ACh in chloroform solution is measured to be 3.65 kcal/mol in the presence of chloride anion by nuclear magnetic resonance spectroscopy, and that in water is estimated to be much greater ( approximately 6 kcal/mol).

Acetylcholine↗

PubMed2003

Interaction of E. coli outer-membrane protein A with sugars on the receptors of the brain microvascular endothelial cells.

Esherichia coli, the most common gram-negative bacteria, can penetrate the brain microvascular endothelial cells (BMECs) during the neonatal period to cause meningitis with significant morbidity and mortality. Experimental studies have shown that outer-membrane protein A (OmpA) of E. coli plays a key role in the initial steps of the invasion process by binding to specific sugar moieties present on the glycoproteins of BMEC. These experiments also show that polymers of chitobiose (GlcNAcbeta1-4GlcNAc) block the invasion, while epitopes substituted with the L-fucosyl group do not. We used HierDock computational technique that consists of a hierarchy of coarse grain docking method with molecular dynamics (MD) to predict the binding sites and energies of interactions of GlcNAcbeta1-4GlcNAc and other sugars with OmpA. The results suggest two important binding sites for the interaction of carbohydrate epitopes of BMEC glycoproteins to OmpA. We identify one site as the binding pocket for chitobiose (GlcNAcbeta1-4GlcNAc) in OmpA, while the second region (including loops 1 and 2) may be important for recognition of specific sugars. We find that the site involving loops 1 and 2 has relative binding energies that correlate well with experimental observations. This theoretical study elucidates the interaction sites of chitobiose with OmpA and the binding site predictions made in this article are testable either by mutation studies or invasion assays. These results can be further extended in suggesting possible peptide antagonists and drug design for therapeutic strategies.

Bacterial Outer Membrane Proteins↗

PubMed2002

Assembling phenomena of calix[4]hydroquinone nanotube bundles by one-dimensional short hydrogen bonding and displaced pi-pi stacking.

Using the computer-aided molecular design approach, we recently reported the synthesis of calix[4]hydroquinone (CHQ) nanotube arrays self-assembled with infinitely long one-dimensional (1-D) short hydrogen bonds (H-bonds) and aromatic-aromatic interactions. Here, we assess various calculation methods employed for both the design of the CHQ nanotubes and the study of their assembly process. Our calculations include ab initio and density functional theories and first principles calculations using ultrasoft pseudopotential plane wave methods. The assembly phenomena predicted prior to the synthesis of the nanotubes and details of the refined structure and electronic properties obtained after the experimental characterization of the nanotube crystal are reported. For better characterization of intriguing 1-D short H-bonds and exemplary displaced pi-pi stacks, the X-ray structures have been further refined with samples grown in different solvent conditions. Since X-ray structures do not contain the positions of H atoms, it is necessary to analyze the system using quantum theoretical calculations. The competition between H-bonding and displaced pi-pi stacking in the assembling process has been clarified. The IR spectroscopic features and NMR chemical shifts of 1-D short H-bonds have been investigated both experimentally and theoretically. The dissection of the two most important interaction components leading to self-assembly processes would help design new functional materials and nanomaterials.

Calixarenes↗

PubMed2002

An electrochemically controllable nanomechanical molecular system utilizing edge-to-face and face-to-face aromatic interactions.

[formula: see text] A new molecular system, 2,11-dithio[4,4]metametaquinocyclophane containing a quinone moiety, was designed and synthesized. As the quinone moiety can readily be converted into an aromatic pi-system (hydroquinone) upon reduction, the nanomechanical molecular cyclophane system exhibits a large flapping motion like a molecular flipper from the electrochemical redox process. The conformational changes upon reduction and oxidation are caused by changes of nonbonding interaction forces (devoid of bond formation/breaking) from the edge-to-face to face-to-face aromatic interactions and vice versa, respectively.

Journal Article↗

PubMed2002

Tripodal nitro-imidazolium receptor for anion binding driven by (C-H)+- - -X- hydrogen bonds.

[structure: see text] A positively charged tripodal receptor with nitro groups in the imidazolium rings was designed, synthesized, and characterized for its anion binding strength. The receptor shows strong affinity and high selectivity for Cl- through (C-H)+- - -X(-) hydrogen bonds wherein charge-charge and charge-dipole electrostatic interactions dominate. The association constant with chloride anion in a 9:1 mixture of acetonitrile-d3 and DMSO-d6 is measured to be 1.1 x 10(6) M(-1). The receptor also shows reasonably high affinity toward H2PO4-.

Anions↗

PubMed2002

Trifluoroethanol increases the stability of Delta(5)-3-ketosteroid isomerase. 15N NMR relaxation studies.

In the equilibrium unfolding process of Delta(5)-3-ketosteroid isomerase from Pseudomonas testosteroni by urea, it was observed that the enzyme stability increases by 2.5 kcal/mol in the presence of 5% trifluoroethanol (TFE). To elucidate the increased enzyme stability by TFE, the backbone dynamics of Delta(5)-3-ketosteroid isomerase were studied in the presence and absence of 5% TFE by (15)N NMR relaxation measurements, and the motional parameters (S(2), tau(e), and R(ex)) were extracted from the relaxation data using the model-free formalism. The presence of 5% TFE causes little change or a slight increase in the order parameters (S(2)) for a number of residues, which are located mainly in the dimer interface region. However, the majority of the residues exhibit reduced order parameters in the presence of 5% TFE, indicating that high frequency (pico- to nanosecond) motions are generally enhanced by TFE. The results suggest that the entropy can be an important factor for the enzyme stability, and the increase in entropy by TFE is partially responsible for the increased stability of Delta(5)-3-ketosteroid isomerase.

Diffusion↗

PubMed2002

Catalytic mechanism of enzymes: preorganization, short strong hydrogen bond, and charge buffering.

During the past decade, there has been much debate about the enormous catalytic rate enhancement observed in enzymatic reactions involving carbanion intermediates. Our recent theoretical study has demonstrated the importance of the short strong hydrogen bond (SSHB) in the enzymatic reactions. Nevertheless, other recent theoretical studies espouse the role of preorganization over that of the SSHB. To achieve a consensus on this issue and to find the truth, a more clarified explanation must be given. To this end, we have carried out an elaborate analysis of these enzymatic reactions. We here clarify that the catalytic mechanism needs to be explained with three important factors, viz., SSHB, preorganization, and charge buffering/dissipation. Since the charge buffering role is different from the commonly used concepts of the SSHB and preorganization (unless these definitions are expanded), we stress that the charge buffering role of the catalytic residues is an important ingredient of the enzymatic reaction in reducing the level of accumulation of the negative charge on the substrate during the reaction process. This charge reduction is critical to the lowering of activation barriers and the stabilization of intermediates.

Buffers↗

PubMed2002

A new type of ionophore family utilizing the cation-olefinic pi interaction: theoretical study of [n]beltenes.

The possible utilization of [n]beltenes as a new family of ionophores, which exhibit a cation-olefinic pi type of interaction in contrast to the cation-aromatic pi type of interaction exhibited by [n]collarenes, has been investigated using both ab initio calculations and molecular dynamic simulations. Like [n]collarenes, n ethene groups are linked by -CH(2)- linkages in the [n]beltenes. Our calculations indicate that these [n]beltenes exhibit strong binding affinities and high selectivity for alkali metal cations ([5]beltene to Li(+), [6]beltene to Na(+), [7]beltene to Na(+) and K(+), [8]beltene to K(+) and Rb(+), and [9]beltene to Cs(+) and Rb(+)). Compared to [n]collarenes, [n]beltenes are expected to have a finer ion selectivity because their cavity sizes can be varied with integral number n, while that of the former can be varied with an even number n. Suitable substituents could be employed to enhance both the binding and specificity of various sizes of [n]beltenes to different cations, as well as to increase the solubility.

Journal Article↗