• Bulletin of the Korean Chemical Society
• /
• v.34 no.10
• /
• pp.3137-3140
• /
• 2013

• Genomics & Informatics
• /
• v.1 no.1
• /
• pp.7-19
• /
• 2003

The latest measure of the relative evolutionary age of protein structure families was applied (based on taxonomic diversity) using the protein structural interactome map (PSIMAP). It confirms that, in general, protein domains, which are hubs in this interaction network, are older than protein domains with fewer interaction partners. We apply a hypothesis of 'biological network evolution' to explain the positive correlation between interaction and age. It agrees to the previous suggestions that proteins have acquired an increasing number of interaction partners over time via the stepwise addition of new interactions. This hypothesis is shown to be consistent with the scale-free interaction network topologies proposed by other groups. Closely co-evolved structural interaction and the dynamics of network evolution are used to explain the highly conserved core of protein interaction pathways, which exist across all divisions of life.

• Journal of the Korean Magnetic Resonance Society
• /
• v.22 no.4
• /
• pp.76-81
• /
• 2018

Investigation of the protein-protein interaction mode at atomic resolution is essential for understanding on the underlying functional mechanisms of proteins as well as for discovering druggable compounds blocking deleteriou interprotein interactions. Solution NMR spectroscopy provides accurate and precise information on intermolecular interactions even for weak and transient interactions, and it is also markedly useful for examining the change in the conformation and dynamics of target proteins upon binding events. In this mini-review, we comprehensively describe three unique and powerful methods of solution NMR spectroscopy, paramagnetic relaxation enhancement (PRE), pseudo-contact shift (PCS), and residual dipolar coupling (RDC), for the study on protein-protein interactions.

• Proceeding of EDISON Challenge
• /
• 2014.03a
• /
• pp.237-249
• /
• 2014

Deposition of amyloid-${\beta}$ ($A{\beta}$) proteins is the conventional pathological hallmark of Alzheimer's disease (AD). The $A{\beta}$ protein formed from the amyloid precursor protein is predominated by the 40 residue protein ($A{\beta}40$) and by the 42 residue protein ($A{\beta}42$). While $A{\beta}40$ and $A{\beta}42$ differ in only two amino acid residues at the C-terminal end, $A{\beta}42$ is much more prone to aggregate and exhibits more neurotoxicity than $A{\beta}40$. Here, we investigate the molecular origin of the difference in the aggregation propensity of these two proteins by performing fully atomistic, explicit-water molecular dynamics simulations. Then, it is followed by the solvation thermodynamic analysis based on the integral-equation theory of liquids. We find that $A{\beta}42$ displays higher tendency to adopt ${\beta}$-sheet conformations than $A{\beta}40$, which would consequently facilitate the conversion to the ${\beta}$-sheet rich fibril structure. Furthermore, the solvation thermodynamic analysis on the simulated protein conformations indicates that $A{\beta}42$ is more hydrophobic than $A{\beta}40$, implying that the surrounding water imparts a larger thermodynamic driving force for the self-assembly of $A{\beta}42$. Taken together, our results provide structural and thermodynamic grounds on why $A{\beta}42$ is more aggregation-prone than $A{\beta}40$ in aqueous environments.

• Bulletin of the Korean Chemical Society
• /
• v.31 no.6
• /
• pp.1519-1526
• /
• 2010

The behavior of peptide or protein solutes in saline aqueous solution is a fundamental topic in physical chemistry. Addition of ions can strongly alter the thermodynamic and physical properties of peptide molecules in solution. In order to study the effects of added ionic salts on protein conformation and dynamics, we have used the molecular dynamics (MD) simulations to investigate the behavior of Staphylococcus aureus Hfq protein under two different ionic concentrations: 0.1 M NaCl and 1.0 M NaCl in presence and absence of RNA (a hepta-oligoribonucleotide AU5G). Hfq, a global regulator of gene expression is highly conserved and abundant RNA-binding protein. It is already reported that in vivo the increase of ionic strength results in a drastic reduction of Hfq affinity for $Q{\beta}$ RNA and reduces the tendency of aggregation of Escherichia coli host factor hexamers. Our results revealed the crucial role of 0.1 M NaCl Hfq system on the bases with strong hydrogen bonding interactions and by stabilizing the aromatic stacking of Tyr42 residue of the adjacent subunits/monomers with the adenine and uridine nucleobases. An increase in RNA pore diameter and weakened compactness of the Hfq-RNA complex was clearly observed in 1.0 M NaCl Hfq system with bound RNA. Aggregation of monomers in Hfq and the interaction of Hfq with RNA are greatly affected due to the presence of high ionic strength. Higher the ionic concentration, weaker is the aggregation and interaction. Our results were compatible with the experimental data and this is the first theoretical report for the experimental study done in 1980 by Uhlenbeck group for the present system.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.28 no.1
• /
• pp.178-190
• /
• 1999

This study was conducted to develop a simulation model for the growth dynamics of pigs and to describe quantitatively protein deposition depending on the amino acid composition of feed protein. In the model it is assumed that the essential processes that determine the utilization of feed protein in the whole body are protein synthesis, breakdown of protein, and oxidation of amino acid. Besides, it is also assumed that occurrence of protein deposition depends on genetic potential and amino acid composition of feed protein. The genetic potential for the protein deposition is the maximum capacity of protein synthesis, being dependent on the protein mass of the whole body. To describe the effect of amino acid composition of feed on the protein deposition, a factor, which consist of ten amino acid functions and lie between 0 and 1, is introduced. Accordingly a model was developed, which is described with 15 flux equations and 11 differential equations and is composed of two compartments. The model describes non linear structure of the protein utilization system of an organism, which is in non steady state. The objective function for the simulation was protein deposition(g/day) cal culated according to the empirical model, PAF(product of amino acid functions) of Menke. The mean of relative difference between the simulated protein deposition and PAF calculated values, lied in a range of 11.8%. The simulated protein synthesis and breakdown rates(g/day) in the whole body showed a parallel behavior in the course of growth.

• Journal of the Korean Magnetic Resonance Society
• /
• v.18 no.1
• /
• pp.1-4
• /
• 2014

It is generally understood that protein-protein interactions proceed via transient encounter complexes that rapidly evolve into the functional stereospecific complex. Direct detection and characterization of the encounter complexes, however, been difficult due to their low population and short lifetimes. Recent application of NMR paramagnetic relaxation enhancement first visualized the structures of the encounter complex ensemble, and allowed the characterization of their physicochemical properties. Further, rational protein mutations that perturbed the encounter complex formation provided a clue to the target search pathway during protein-protein association. Understanding the structure and dynamics of encounter complexes will provide useful information on the mechanism of protein association.

• Bulletin of the Korean Chemical Society
• /
• v.30 no.4
• /
• pp.913-916
• /
• 2009

Femtosecond vibrational spectroscopy was used to probe the dynamics of CO rebinding to hemoglobin (Hb), denatured by 4.0 M GdnHCl in $D_2O# at 283 K, after photolysis of HbCO. The stretching mode of $^{13}CO$ bound to the denatured $Hb^{13}CO$ showed a single band centered at 1922 $cm^{-1}$, indistinguishable from that of denatured $Mb^{13}CO$. Geminate rebinding of CO to the denatured Hb was accelerated more than 1000 times, suggesting that the native structure of the Hb is required to suppress efficient geminate rebinding of CO, as is the case in Mb. The geminate yield and rate for CO rebinding are almost the same in both the denatured Hb and Mb. Similarity in the equilibrium spectrum and rebinding dynamics of CO indicates that the state of the denatured Hb is very similar to that of the denatured Mb. In the denatured Hb, quaternary contact of the protein is likely severed, with the denatured protein existing as an independent subunit much like Mb.

• Bulletin of the Korean Chemical Society
• /
• v.26 no.1
• /
• pp.151-156
• /
• 2005

The conformational dynamics of heme pocket, a small vacant site near the binding site of heme proteins -myoglobin (Mb) and hemoglobin (Hb), was investigated after photolysis of carbon monoxide from MbCO and HbCO in D$_2$O solution at 283 K by probing time-resolved vibrational spectra of photolyzed CO. Two absorption bands, arising from CO in the heme pocket, evolve nonexponentially in time. The band at higher energy side blue shifts and broadens with time and the one at lower energy side narrows significantly with a negligible shift. These spectral evolutions are induced by protein conformational changes following photolysis that modify structure and electric field of heme pocket, and ligand dynamics in it. The conformational changes affecting the spectrum of photolyzed CO in heme pocket likely modulates ligand-binding activity.

• Journal of Integrative Natural Science
• /
• v.7 no.2
• /
• pp.75-78
• /
• 2014

Computer-aided drug design uses computational chemistry to discover, enhance, or study drugs and related biologically active molecules. It is now proved to be effective in reducing costs and speeding up drug discovery. In this short review, we discussed on the importance of combining molecular docking and molecular dynamics simulation methodologies. We also reviewed the importance of protein flexibility, refinement of docked complexes using molecular dynamics and the use of free energy calculations for the calculation of accurate binding energies has been reviewed.