• The Plant Pathology Journal
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• v.33 no.6
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• pp.529-542
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• 2017

Control of plant diseases is largely dependent on use of agrochemicals. However, there are widening gaps between our knowledge on plant diseases gained from genetic/mechanistic studies and rapid translation of the knowledge into target-oriented development of effective agrochemicals. Here we propose that the time is ripe for computer-aided drug discovery/design (CADD) in molecular plant pathology. CADD has played a pivotal role in development of medically important molecules over the last three decades. Now, explosive increase in information on genome sequences and three dimensional structures of biological molecules, in combination with advances in computational and informational technologies, opens up exciting possibilities for application of CADD in discovery and development of agrochemicals. In this review, we outline two categories of the drug discovery strategies: structure- and ligand-based CADD, and relevant computational approaches that are being employed in modern drug discovery. In order to help readers to dive into CADD, we explain concepts of homology modelling, molecular docking, virtual screening, and de novo ligand design in structure-based CADD, and pharmacophore modelling, ligand-based virtual screening, quantitative structure activity relationship modelling and de novo ligand design for ligand-based CADD. We also provide the important resources available to carry out CADD. Finally, we present a case study showing how CADD approach can be implemented in reality for identification of potent chemical compounds against the important plant pathogens, Pseudomonas syringae and Colletotrichum gloeosporioides.

• Journal of Biomedical Engineering Research
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• v.43 no.2
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• pp.71-80
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• 2022

The interaction between dual-ligand decorated particle-based delivery system and target cell under shear flow is predicted using probability model developed. We assumed the two kinds of ligand are decorated on the surface of the particle with 10% length difference. Fixed with other biophysical parameters, a study on the particle-cell interaction for the different non-specific interaction parameter is performed. To induce the firm adhesion, short ligand-receptor should be engaged. Also, it is shown that the rational design of ligand-receptor interaction, including receptor number, specific interaction parameter, kinds of ligand-receptor, etc., should be considered.

• Journal of Integrative Natural Science
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• v.3 no.3
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• pp.143-147
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• 2010

Since it is of great importance to know how a ligand binds to a receptor, there have been a lot of efforts to improve the quality of prediction of docking poses. Earlier efforts were focused on improving search algorithm and scoring function in a docking program resulting in a partial improvement with a lot of variations. Although these are basically very important and essential, more tangible improvements came from the reduction of search space. In a normal docking study, the approximate active site is assumed to be known. After defining active site, scoring functions and search algorithms are used to locate the expected binding pose within this search space. A good search algorithm will sample wisely toward the correct binding pose. By careful study of receptor structure, it was possible to prioritize sub-space in the active site using "receptor-based pharmacophores" or "hot spots". In a sense, these techniques reduce the search space from the beginning. Further improvements were made when the bound ligand structure is available, i.e., the searching could be directed by molecular similarity using ligand information. This could be very helpful to increase the accuracy of binding pose. In addition, if the biological activity data is available, docking program could be improved to the level of being useful in affinity prediction for a series of congeneric ligands. Since the number of co-crystal structures is increasing in protein databank, "Ligand-Guided Docking" to reduce the search space would be more important to improve the accuracy of docking pose prediction and the efficiency of virtual screening. Further improvements in this area would be useful to produce more reliable docking programs.

• Journal of Integrative Natural Science
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• v.2 no.2
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• pp.55-58
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• 2009

A ligand-receptor docking program is an indispensible tool in modern pharmaceutical design. An accurate prediction of small molecular docking pose to a receptor is essential in drug design as well as molecular recognition. An effective docking program requires the ability to locate a correct binding pose in a surprisingly complex conformational space. However, there is an inherent difficulty to predict correct binding pose. The odds are more demanding than finding a needle in a haystack. This mainly comes from the flexibility of both ligand and receptor. Because the searching space to consider is so vast, receptor rigidity has been often applied in docking programs. Even nowadays the receptor may not be considered to be fully flexible although there have been some progress in search algorithm. Improving the efficiency of searching algorithm is still in great demand to explore other applications areas with inherently flexible ligand and/or receptor. In addition to classical search algorithms such as molecular dynamics, Monte Carlo, genetic algorithm and simulated annealing, rather recent algorithms such as tabu search, stochastic tunneling, particle swarm optimizations were also found to be effective. A good search algorithm would require a good balance between exploration and exploitation. It would be a good strategy to combine algorithms already developed. This composite algorithms can be more effective than an individual search algorithms.

• Journal of the Korean Society of Industry Convergence
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• v.3 no.1
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• pp.77-82
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• 2000

The stereoselective ligand exchange reaction of trans-$[Co(SS-epm)Cl_2]^+$ and racemic propane-1,2-diamine (rac-pn) produces the complex that is identified as $[CO(N)_6]^{3+}$ type of $[Co(SS-epm)(pn)]^{3+}$ by absorption spectrum. It is conceivable that the reaction mechanism involves substitution and isomerization. The calculated and experimentally determined ratios of the complexed enantiomeric substrates at equilibrium were as follows: $[Co(SS-epm)(pn)]^{3+}$,calcd 32 % / 68 %, exptl 19 % / 81 % R-pn / S-pn. It has been shown that the employment of molecular mechanics calculations as a predictive tool may lead to the design of chiral complexes that may be applied to the separation of racemic mixtures of simple bidentate ligands.

• Bulletin of the Korean Chemical Society
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• v.32 no.7
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• pp.2433-2442
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• 2011

The three dimensional quantitative structure activity relationship (3D QSAR) models were developed using Comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and docking studies. The fit of Quinazolinone antifolates inside the active site of modeled bovine dihydrofolate reductase (DHFR) was assessed. Both ligand based (LB) and receptor based (RB) QSAR models were generated, these models showed good internal and external statistical reliability that is evident from the $q^2_{loo}$, $r^2_{ncv}$ and $r^2_{pred}$. The identified key features enabled us to design new Quinazolinone analogues as DHFR inhibitors. This study is a building bridge between docking studies of homology modeled bovine DHFR protein as well as ligand and target based 3D QSAR techniques of CoMFA and CoMSIA approaches.

• Journal of the Korean Magnetic Resonance Society
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• v.6 no.2
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• pp.94-102
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• 2002

An interesting recent application of intermolecular NOE experiment is the saturation transfer difference NMR(STD-NMR) method that is useful in screening compound libraries to identify bio-active ligands. This technique also identifies the group epitopes of the bound ligand in a reversibly forming protein-ligand complex. We present here a complete relaxation and conformational exchange matrix (CORCEMA) theory (Moseley et al., J. Magn. Reson. B, 108, 243-261 (1995)) applicable for the STD-NMR experiment. Using some ideal model systems we have analyzed the factors that influence the STD intensity changes in the ligand proton NMR spectrum when the resonances from some protons on the receptor protein are saturated. These factors will be discussed and some examples of its application in some model systems will be presented. This CORCEMA theory for STD-NMR and the associated algorithm are useful in a quantitative interpretation of the STD-NMR effects, and are likely to be useful in structure-based drug design efforts. They are also useful in a quantitative characterization of protein-protein (or protein-nucleic acid) contact surfaces from an intermolecular cross-saturation NMR experiment.

• Carbon letters
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• v.4 no.1
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• pp.1-9
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• 2003

Recently, the control of pore-characteristics of nano-porous materials has been studied extensively because of their unique applications, which includes size-selective separation, gas adsorption/storage, heterogeneous catalysis, etc. The most widely adopted techniques for controlling pore characteristics include the utilization of pillar effect by metal oxide and of templates such as zeolites. More recently, coordination polymers constructed by transition metal ions and bridging organic ligands have afforded new types of nano-porous materials, porous metal-organic framework(porous MOF), with high degree and uniformity of porosity. The pore characteristics of these porous MOFs can be designed by controlling the coordination number and geometry of selected metal, e.g transition metal and rare-earth metal, and the size, rigidity, and coordination site of ligand. The synthesis of porous MOF by the assembly of metal ions with di-, tri-, and poly-topic N-bound organic linkers such as 4,4'-bipyridine(BPY) or multidentate linkers such as carboxylates, which allow for the formation of more rigid frameworks due to their ability to aggregate metal ions into M-O-C cluster, have been reported. Other porous MOF from co-ligand system or the ligand with both C-O and C-N type linkage can afford to control the shape and size of pores. Furthermore, for the rigidity and thermal stability of porous MOF, ring-type ligand such as porphyrin derivatives and ligands with ability of secondary bonding such as hydrogen and ionic bonding have been studied.

• Fibers and Polymers
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• v.2 no.2
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• pp.51-57
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• 2001

Tissue engineering is one exciting approach to treat patients who need a new organ or tissue. A critical element in this approach is the polymer scaffold, as it provides a space for new tissue formation and mimics many roles of natural extra-cellular matrices. In this review, we describe several design parameters of polymer matrices that can significantly affect cellular behavior, as well as various polymers which are frequently used to date or potentially useful in many tissue engineering applications. Interactions between cells and polymer scaffolds, including specific receptor-ligand interactions, physical and degradation feature of the scaffolds, and delivery of soluble factors, should be considered in the design and tailoring of appropriate polymer matrices to be used in tissue engineering applications, as these interactions control the function and structure of engineered tissues.

• 한국생물공학회:학술대회논문집
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• 2005.10a
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• pp.1006-1006
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• 2005