Inversion Barriers of Methylsilole and Methylgermole Monoanions

Pak, Youngshang,Ko, Young Chun,Sohn, Honglae Korean Chemical Society 2012 Bulletin of the Korean Chemical Society Vol.33 No.12

Density functional MO calculations for the methylsilole anion of $[C_4H_4SiMe]^-$ and methylgermole anion of $[C_4H_4SiMe]^-$ at the B3LYP (full)/6-311+$G^*$ level (GAUSSIAN 94) were carried out and characterized by frequency analysis. The ground state structure for the methylsilole anion and methylgermole anion is that the methyl group is pyramidalized with highly localized structure. The difference between the calculated $C_{\alpha}-C_{\beta}$ and $C_{\beta}-C_{\beta}$ distances are 9.4 and 11.5 pm, respectively. The E-Me vector forms an angle of $67.9^{\circ}$ and $78.2^{\circ}$ with the $C_4E$ plane, respectively. The optimized structures of the saddle point state for the methylsilole anion and methylgermole anion have been also found as a planar with highly delocalized structure. The optimized $C_{\alpha}-C_{\beta}$ and $C_{\beta}-C_{\beta}$ distances are nearly equal for both cases. The methyl group is located in the plane of $C_4E$ ring and the angle between the E-Me vector and the $C_4E$ plane for the methylsilole anion and methylgermole anion is $2.0^{\circ}$ and $2.3^{\circ}$, respectively. The energy difference between the ground state structure and the transition state structure is only 5.1 kcal $mol^{-1}$ for the methylsilole anion. However, the energy difference of the methylgermole anion is 14.9 kcal $mol^{-1}$, which is much higher than that for the corresponding methylsilole monoanion by 9.8 kcal $mol^{-1}$. Based on MO calculations, we suggest that the head-to-tail dimer compound, 4, result from [2+2] cycloaddition of silicon-carbon double bond character in the highly delocalized transition state of 1. However, the inversion barrier for the methylgermole anion is too high to dimerize.

Computational Study of Human Calcitonin (hCT) Oligomer

Youngshang Pak,Jungho Shin,장순민 대한화학회 2009 Bulletin of the Korean Chemical Society Vol.30 No.12

We have performed long time REMD simulation on 15-19 residues of human calcitonin hormone (DFNKF) which is known to form highly ordered amyloid fibril. The simulation started from randomly oriented multiple DFNKF strand. Using all-atom level simulations with the generalized Born solvation (GB) model (param99MOD3), we observed spontaneous formation of β-sheet for tetramer. Interestingly, the current simulation gives anti-parallel sheet as a major conformation, consistent with experiments. The major interaction stabilizing the anti-parallel sheet seems to be the inter-strand hydrogen bond.

Large Tunneling Effecton the Hydrogen Transfer inBis(μ-oxo)dicopper Enzyme: A Theoretical Study

Park, Kisoo,Pak, Youngshang,Kim, Yongho American Chemical Society 2012 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.134 No.7

<P>Type-III copper-containing enzymes have dicopper centers in their active sites and exhibit a novel capacity for activating aliphatic C-H bonds in various substrates by taking molecular oxygen. Dicopper enzyme models developed by Tolman and co-workers reveal exceptionally large kinetic isotope effects (KIEs) for the hydrogen transfer process, indicating a significant tunneling effect. In this work, we demonstrate that variational transition state theory allows accurate prediction of the KIEs and Arrhenius parameters for such model systems. This includes multidimensional tunneling based on state-of-the-art quantum-mechanical calculations of the minimum-energy path (MEP). The computational model of bis(mu-oxo)dicopper enzyme consists of 70 atoms, resulting in a 204-dimensional potential energy surface. The calculated values of E-a(H) - E-a(D), A(H)/A(D), and the KIE at 233 K are -1.86 kcal/mol, 0.51, and 28.1, respectively, for the isopropyl ligand system. These values agree very well with experimental values within the limits of experimental error. For the representative tunneling path (RTP) at 233 K, the pre- and post-tunneling configurations are 3.3 kcal/mol below the adiabatic energy maximum, where the hydrogen travels 0.54 angstrom by tunneling. We found that tunneling is very efficient for hydrogen transfer and that the RTP is very different from the MEP. It is mainly heavy atoms that move as the reaction proceeds from the reactant complex to the pretunneling configuration, and the hydrogen atom suddenly hops at that point.</P>

Stimulated reversal of the strong adhesion of catechol onto a silica surface

Hyeonjun Kim,Youngshang Pak 대한화학회 2022 Bulletin of the Korean Chemical Society Vol.43 No.2

Marine mussels permanently adhere to various surfaces via catechol (1,2-dihydroxybenzene) functional groups. Such biofouling causes adverse effects, including the corrosion and dragging of a marine vessel. By using the density functional theory, we show an electrical stimulus detach a catechol molecule that strongly adhered to a silica surface. A moderate electric field significantly decreases the binding energy of catechol adhered to a dry or wet silica surface.

Computational study of the pKa values of a modified G·C base pair in duplex DNA

Hyeonjun Kim,Youngshang Pak 대한화학회 2022 Bulletin of the Korean Chemical Society Vol.43 No.2

During the demethylation of 5-methyl cytosine residues in duplex DNAs, formyl or carboxyl cytosines are produced and these modified cytosines are preferentially recognized and excised by the thymine DNA glycosylase (TDG). It has been suggested that the TDG detects a soft spot created by weakening of the hydrogen bond of a G·C base pair (bp). Such bp destabilization is ascribed to the presence of electron-withdrawing 5-formyl or 5-carboxyl group in the modified cytosine. Previously, this bp weakening was linked to reduced values of nucleoside molecules. However, the values of nucleosides can deviate from those of duplex DNAs. Thus, to improve agreement with experiments, the corresponding values for DNA environments are needed. In this computational study, we report two values of the N3- and the C5-carboxyl sites in the 5-carboxyl cytosine residue in a duplex DNA that enable more reasonable interpretations of previous experimental data.

Free-Energy Landscape of a Thrombin-Binding DNA Aptamer in Aqueous Environment

Kim, Eunae,Yang, Changwon,Pak, Youngshang American Chemical Society 2012 Journal of chemical theory and computation Vol.8 No.11

<P>Thrombin-binding aptamer (TBA-15) is a single-stranded 15-mer oligonucleotide that has a wide range of biomedical applications. In the presence of metal cations of proper sizes, this aptamer displays G-quadruplexes with a single cation enclosed at its central binding site when it is completely folded. To understand how this aptamer folds into its stable three-dimensional structure in the presence of K<SUP>+</SUP> ions, we carried out free-energy calculations using the state-of-art replica exchange molecular dynamics simulation (REMD) at the all-atom level. The resulting free energy map revealed that TBA-15 follows a two-state folding behavior with a substantially large folding barrier of 6 kcal/mol at ambient temperature. Our simulation showed that the intervening TGT-loop, which is located in the middle of the TBA-15 sequence, virtually remains intact regardless of folding and unfolding states. Furthermore, in the conserved TGT-loop structure, the base-pair stacking of G8 and T9 induces the native-like base orientations of G6 and G10 pertaining to the upper G-quadrant. This stacking interaction enhances the loop stability and reduces its dynamic fluctuations. Interestingly, for the G-stem to fold into its native state, the aggregation of the G8 and T9 residues in the TGT-loop is a key step for initiating the folding event of the G-stem by capturing a bulky cation.</P>

Potential of Mean Force Simulation by Pulling a DNA Aptamer in Complex with Thrombin

Yang, Changwon,Kim, Eunae,Pak, Youngshang Korean Chemical Society 2012 Bulletin of the Korean Chemical Society Vol.33 No.11

Thrombin binding aptamter (TBA-15) is a 15-mer guanine-rich oligonucleotide. This DNA apamer specifically binds to the thrombin protein involved in blood coagulation. Using extensive umbrella sampling molecular dynamics simulation method at all atom level, we investigated the potential of mean force (PMF) upon pulling the DNA aptamer from the binding mode of aptamer/thrombin complex. From this calculation, the free energy cost for a full dissociation of this aptamer/protein complex is 17 kcal/mol, indicating a substantial binding affinity of TBA-15. Interestingly, this PMF reveals noticeable plateau regions along the pulling coordinate. Possible structural changes of this complex in the plateau were investigated in details.

Probing α/β Balances in Modified Amber Force Fields from a Molecular Dynamics Study on a ββα Model Protein (1FSD)

Changwon Yang,김은애,Youngshang Pak 대한화학회 2014 Bulletin of the Korean Chemical Society Vol.35 No.6

1FSD is a 28-residue designed protein with a ββα motif. Since this protein displays most essential features of protein structures in such a small size, this model protein can be an outstanding system for evaluating the balance in the propensity of the secondary structures and the quality of all-atom protein force fields. Particularly, this protein would be difficult to fold to its correct native structure without establishing proper balances between the secondary structure elements in all-atom energy functions. In this work, a series of the recently optimized five amber protein force fields [ff03*, ff99sb*-ildn, ff99sb-φ'-ildn, ff99sb-nmr1-ildn, ff99sb-ΦΨ(G24, CS)-ildn] were investigated for the simulations of 1FSD using a conventional molecular dynamics (MD) and a biased-exchange meta-dynamics (BEMD) methods. Among those tested force fields, we found that ff99sb-nmr1-ildn and ff99sb-ΦΨ(G24, CS)-ildn are promising in that both force fields can locate the native state of 1FSD with a high accuracy (backbone rmsd ≤ 1.7 Å) in the global free energy minimum basin with a reasonable energetics conforming to a previous circular dichroism (CD) experiment. Furthermore, both force fields led to a common set of two distinct folding pathways with a heterogeneous nature of the transition state to the folding. We anticipate that these force fields are reasonably well balanced, thereby transferable to many other protein folds.

On the Structural Stability of a Short Three Stranded β-sheet Peptide (Betanova): Replica Exchange Molecular Dynamics Simulation Study

장순민,Eunae Kim,Youngshang Pak 대한화학회 2010 Bulletin of the Korean Chemical Society Vol.31 No.8

Canonical Sampling Method for Initial Conditions for Reactive Flux Calculations Using Nose-Hoover Chains

Song Hi Lee*,Youngshang Pak* 대한화학회 2004 Bulletin of the Korean Chemical Society Vol.25 No.4