• Clinical and Experimental Pediatrics
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• 제65권5호
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• pp.239-249
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• 2022

Cells survive and proliferate through complex interactions among diverse molecules across multiomics layers. Conventional experimental approaches for identifying these interactions have built a firm foundation for molecular biology, but their scalability is gradually becoming inadequate compared to the rapid accumulation of multiomics data measured by high-throughput technologies. Therefore, the need for data-driven computational modeling of interactions within cells has been highlighted in recent years. The complexity of multiomics interactions is primarily due to their nonlinearity. That is, their accurate modeling requires intricate conditional dependencies, synergies, or antagonisms between considered genes or proteins, which retard experimental validations. Artificial intelligence (AI) technologies, including deep learning models, are optimal choices for handling complex nonlinear relationships between features that are scalable and produce large amounts of data. Thus, they have great potential for modeling multiomics interactions. Although there exist many AI-driven models for computational biology applications, relatively few explicitly incorporate the prior knowledge within model architectures or training procedures. Such guidance of models by domain knowledge will greatly reduce the amount of data needed to train models and constrain their vast expressive powers to focus on the biologically relevant space. Therefore, it can enhance a model's interpretability, reduce spurious interactions, and prove its validity and utility. Thus, to facilitate further development of knowledge-guided AI technologies for the modeling of multiomics interactions, here we review representative bioinformatics applications of deep learning models for multiomics interactions developed to date by categorizing them by guidance mode.

• Molecules and Cells
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• 제45권7호
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• pp.444-453
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• 2022

Multivalent macromolecular interactions underlie dynamic regulation of diverse biological processes in ever-changing cellular states. These interactions often involve binding of multiple proteins to a linear lattice including intrinsically disordered proteins and the chromosomal DNA with many repeating recognition motifs. Quantitative understanding of such multivalent interactions on a linear lattice is crucial for exploring their unique regulatory potentials in the cellular processes. In this review, the distinctive molecular features of the linear lattice system are first discussed with a particular focus on the overlapping nature of potential protein binding sites within a lattice. Then, we introduce two general quantitative frameworks, combinatorial and conditional probability models, dealing with the overlap problem and relating the binding parameters to the experimentally measurable properties of the linear lattice-protein interactions. To this end, we present two specific examples where the quantitative models have been applied and further extended to provide biological insights into specific cellular processes. In the first case, the conditional probability model was extended to highlight the significant impact of nonspecific binding of transcription factors to the chromosomal DNA on gene-specific transcriptional activities. The second case presents the recently developed combinatorial models to unravel the complex organization of target protein binding sites within an intrinsically disordered region (IDR) of a nucleoporin. In particular, these models have suggested a unique function of IDRs as a molecular switch coupling distinct cellular processes. The quantitative models reviewed here are envisioned to further advance for dissection and functional studies of more complex systems including phase-separated biomolecular condensates.

• IMMUNE NETWORK
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• 제21권6호
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• pp.40.1-40.20
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• 2021

Mycobacteroides abscessus (previously Mycobacterium abscessus; Mabc), one of rapidly growing nontuberculous mycobacteria (NTM), is an important pathogen of NTM pulmonary diseases (NTM-PDs) in both immunocompetent and immunocompromised individuals. Mabc infection is chronic and often challenging to treat due to drug resistance, motivating the development of new therapeutics. Despite this, there is a lack of understanding of the relationship between Mabc and the immune system. This review highlights recent progress in the molecular architecture of Mabc and host interactions. We discuss several microbial components that take advantage of host immune defenses, host defense pathways that can overcome Mabc pathogenesis, and how host-pathogen interactions determine the outcomes of Mabc infection. Understanding the molecular mechanisms underlying host-pathogen interactions during Mabc infection will enable the identification of biomarkers and/or drugs to control immune pathogenesis and protect against NTM infection.

• BMB Reports
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• 제42권1호
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• pp.41-46
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• 2009

Post-transcriptional regulation of mRNA stability by Hu proteins is an important mechanism for tumorigenesis. We focused on the molecular interactions between the HuC protein and AU-rich elements (AREs) to find chemical inhibitors of RNA-protein interactions using RNA electrophoretic mobility shift assay with non-radioactive probes. Screening of 52 natural compounds identified 14 candidate compounds that displayed potent inhibitory activity. Six (quercetin, myricetin, (-)-epigallocatechin gallate, ellagic acid, (-)-epicatechin gallate, and rhamnetin) were categorized as phytochemicals, and their $IC_{50}$ values were low ($0.2-1.8\;{\mu}M$).

• 한국진공학회지
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• 제16권1호
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• pp.52-57
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• 2007

생명현상 발현에 중요한 역할을 하는 생체 분자간 특이적 상호작용을 단분자 수준에서 이해하려는 연구는 매우 중요한 일이다. 나노 바이오 측정기술을 이용하여 여러 복잡한 생명현상을 그 기본 단위인 단일 세포 차원에서 직접 측정하여 응용하려는 시도가 이루어지고 있다. 이런 시도로써, 원자힘 현미경을 이용한 생체분자간의 결합력 측정은 생명현상과 가장 유사한 환경에서 단일 생체 분자간 또는 분자 내 힘을 직접 측정함으로써, 단일 생체분자의 현상을 관찰 할 수 있다는 장점을 가지고 있다. 특히 단분자 힘 분광학을 이용한 단일 생체분자내의 세부 단위체간 상호작용에 대한 연구와 단백질-단백질, 단백질-리간드, DNA-DNA의 분자인지 상호작용에 대한 연구는 많은 생명과학 분야 연구자들의 관심을 끌고 있을 뿐만 아니라 더 나아가 새로운 관련 기술의 개발을 촉진시키고 있다.

• 한국진공학회:학술대회논문집
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• 한국진공학회 2011년도 제41회 하계 정기 학술대회 초록집
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• pp.107-107
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• 2011

Supramolecular structures of anthraquinone molecules on a metallic surface are studied using scanning tunneling microscope (STM) under ultrahigh-vacuum conditions. When we deposited anthraquinone molecules on Au(111) substrate, the molecules formed three different phases (Chevron type, tetragon type and disordered type) on the surface. Based on our STM measurements, we proposed models for the observed molecular structures. Chevrons are consisted of several molecular chains, which make well-ordered two-dimensional islands by some weak interrow interactions and we could observe tetragon structures which make array of (111) metallic surface. each molecular rows in the chevrons are stabilized by two parallel O-H hydrogen bonds and disordered structures are observed 1-dimensional phase with hydrogen bond. First-principles calculations based on density functional theory are performed to reproduce the proposed models. Distances and energy gains for each intermolecular bond are estimated. In this presentation, we explain possible origins of these molecular structures in terms of hydrogen bonds, Van der Waals interactions and molecule-substrate interactions.

• Bulletin of the Korean Chemical Society
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• 제35권1호
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• pp.250-252
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• 2014

Lipoprotein-associated phospholipase A2 (Lp-$PLA_2$) is a crucial enzyme in atherosclerosis as a potential drug target. The most remarkable Lp-$PLA_2$ inhibitory drug is Darapladib. We determined the binding pose of Darapladib to Lp-$PLA_2$ through docking study. Darapladib formed two hydrogen bonding interactions with the side chain of Tyr160 and Gln352 and several pi-pi interactions with aromatic and aliphatic hydrophobic residues of Lp-$PLA_2$. It is known that the dietylpropan-amine moiety of Darapladib has influence on the improvement of its oral bioavailability and we supposed this in our docking results.

• 대한화학회지
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• 제65권2호
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• pp.106-112
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• 2021

12 kinds of (-)-catechin derivatives were designed and synthesized. The catechin derivatives were evaluated their antioxidant activities using DPPH method. Most of them showed good antioxidant activity, particularly compounds 1d, 1e and 1j exhibited more activity than butylated hydroxytoluene (BHT). Molecular docking studies for compounds 1d, 1e and 1j with STAT1 showed not only sufficent characteristics binding cavity but also agreement with the observed biological activity. Acording to docking results, the compounds showed greater than hydrogen bonding, hydrophobic interactions, electrostatic interactions, and Van der Waals interactions as compared to the reference compound. They formed hydrogen bonds with important residues such as Lys566, His568, Leu570, and Phe644. The compounds showed a novel hydrogen bonding interaction with Arg649, which was not reported previously. Our results might suggest the compounds could serve as a novel anti-oxidant agent.

• Bulletin of the Korean Chemical Society
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• 제32권7호
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• pp.2222-2226
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• 2011

Amylase is a digestive enzyme that catalyses the starch into sugar. It has been reported that the green tea flavonoid (or polyphenols) (-)-epigallocatechin 3-gallate (EGCG) inhibits human salivary ${\alpha}$-amylase (HSA) and induced anti-nutritional effects. In this study, we performed docking study for seven EGCG-like flavonoids and HSA to understand the interaction mechanism of HSA and EGCG and suggest new possible flavonoid inhibitors of HSA. As a result, EGCG and (-)-epicatechin gallate (ECG) bind to HSA with complex hydrogen bonding interactions. These hydrogen bonding interactions are important for inhibitory activity of EGCG against HSA. We suggested that ECG can be a potent inhibitor of HSA. This study will be helpful to understand the mechanism of inhibition of HSA by EGCG and give insights to develop therapeutic strategies against diabetes.

• Bulletin of the Korean Chemical Society
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• 제24권6호
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• pp.771-776
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• 2003

The structural and dynamic properties of small n-alkane clusters embedded in a mesoscopic solvent are investigated. The solvent interactions are taken into account through a multi-particle collision operator that conserves mass, momentum and energy and the solvent dynamics is updated at discrete time intervals. The cluster molecules interact among themselves and with the solvent molecules through intermolecular forces. The properties of n-heptane and n-decane clusters interacting with the mesoscopic solvent molecules through repulsive Lennard-Jones interactions are studied as a function of the number of the mesoscopic solvent molecules. Modifications of both the cluster and solvent structure as a result of cluster-solvent interactions are considered. The cluster-solvent interactions also affect the dynamics of the small n-alkane clusters.