https://scholar.dgist.ac.kr/handle/20.500.11750/275 2026-04-04T14:14:45Z https://scholar.dgist.ac.kr/handle/20.500.11750/60155 Title: 코로나바이러스 감염증 COVID-19 치료용 펩타이드 및 이의 용도 Author(s): 이영호; 김민기; 권욱봉; 서소욱; 박송; 민가희; 이주환; 지상호; 장익수; 김상열; 유우경; 김효은; 최재석; 김희연; 박성준; 추효섭; 오명원; 이애리; 강무석; 이경은; 최성균; 최민지 Abstract: The present invention relates to a peptide for treatment of the corona virus infection COVID-19 and a use thereof. In order to make the binding to the new epitope of SARS-CoV2 RBD stronger compared to the peptide (P6) simulating the conventionally known binding site between SARS-CoV RBD and ACE2, the peptide of the present invention includes a new portion added with a novel amino acid sequence fundamentally designed for interaction in the dimension of atoms consisting of the amino acids. Suggested in the present invention is a novel design of a peptide having higher binding affinity than conventionally known peptides, wherein an expanded peptide is creatively designed to additionally interact with charged amino acids of D420 and K458, located at the rear side of the known binding boundary between RBD and hACE2. The peptide of the present invention exhibits high possibility as a therapeutic agent for COVID-19. https://scholar.dgist.ac.kr/handle/20.500.11750/59289 Title: Development of New IL-1R Antagonists with Improved Anti-inflammatory Efficacy Author(s): Kang, Mooseok; Lee, Ae-Ree; Jung, Hyeji; Jang, Gyubin; Kim, Byeongchan; Yoon, Sung-Hyun; Yu, Je-Wook; Ko, Jaewon; Um, Ji Won; Chang, Iksoo Abstract: Background: Anakinra, a recombinant human interleukin-1 receptor antagonist (hIL-1Ra), is a widely used anti-inflammatory biologic for conditions like rheumatoid arthritis and gout. However, its limited potency and dose-dependent side effects restrict broader therapeutic application, highlighting a need for more potent and stable IL-1R antagonists. Methods: To develop improved IL-1R antagonists, we rationally designed six hIL-1Ra variants using structure-guided mutagenesis. Molecular dynamics simulations and thermodynamic integration predicted enhanced binding stability, with an average binding free energy improvement of-7.8 +/- 0.9 kcal/mol compared to wild-type hIL-1Ra (hIL-1Ra WT). We assessed variant functions in microglia-derived HMC-3 cells by measuring IL-1 beta and IL-6 mRNA suppression and evaluated their ability to attenuate IL-1 beta-induced NMDAR hyperactivation in cultured cortical neurons using electrophysiological recordings. In vivo validation was performed using Nlrp3D301N knock-in mice, a model of chronic neuroinflammation. Results: All six hIL-1Ra variants demonstrated enhanced anti-inflammatory activity, suppressing IL-1 beta and IL-6 expression by 25-53% in HMC-3 cells. The E127Q variant exhibited the greatest efficacy. In primary cultured neurons, hIL-1Ra E127Q more effectively inhibited IL-1 beta-induced NMDAR-mediated postsynaptic responses at lower concentrations than hIL-1Ra WT. Furthermore, acute administration of hIL-1Ra E127Q, but not hIL-1Ra WT, reversed elevated NMDAR activity in the medial prefrontal cortex of Nlrp3D301N knock-in mice. Conclusion: This study successfully developed next-generation hIL-1Ra variants with superior receptor binding and anti-inflammatory activity. E127Q emerged as a promising therapeutic candidate, effectively attenuating inflammatory signaling and neuroinflammatory responses both in vitro and in vivo. These findings underscore the significant therapeutic potential of engineered IL-1R antagonists for treating inflammation-driven neurological and systemic disorders, paving the way for improved anti-inflammatory therapies. 2025-12-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/59013 Title: Spontaneous formation of oligomers and fibrils in large scale molecular dynamics simulations of peptides Author(s): Hall, Carol; Cheon, Moo Kyung; Latshaw, David; Chang, Iksoo Abstract: Protein aggregation is associated with serious and eventually-fatal neurodegenerative diseases including Alzheimer’s and Parkinson’s. While atomic resolution molecular dynamics simulations have been useful in this regard, they are limited to examination of either oligomer formation by a small number of peptides or analysis of the stability of a moderate number of peptides placed in trial or known experimental structures. We describe large scale intermediate-resolution molecular dynamics simulations of the spontaneous formation of fibrils by systems containing large numbers ( 48-96) of peptides including A-beta (16-22),( 17-42), (1-40) and (1-42) . We trace out the aggregation process from an initial configuration of random coils to oligomers and then to proto-filaments with cross-β structures and demonstrate how kinetics dictates the structural details of the fully formed fibril. Fibrillization kinetics depends strongly on the temperature. Nucleation and templated growth via monomer addition occur at and near a transition temperature above which fibrils are unlikely to form. Oligomeric merging and structural rearrangement are observed at lower temperatures. We also examine the influence of crowding agents on oligomerization and fibrillization. Structural details of the fibrillar structures formed by the shorter peptides including intra-strand and inter-sheet distance and structure and the dependence of twist on the number of layers are consistent with those from experiments. Movies of the aggregation process on a molecular level will be shown. 2015-03-21T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/58294 Title: Wavenumber-dependent transmission of subthreshold waves on electrical synapses network model of Caenorhabditis elegans Author(s): Chang, Iksoo; Chung, Taegon; Kim, Sangyeol Abstract: Recent experimental studies showed that electrically coupled neural networks like in mammalian inferior olive nucleus generate synchronized rhythmic activity by the subthreshold sinusoidal-like oscillations of the membrane voltage. Understanding the basic mechanism and its implication of such phenomena in the nervous system bears fundamental importance and requires preemptively the connectome information of a given nervous system. Inspired by these necessities of developing a theoretical and computational model to this end and, however, in the absence of connectome information for the inferior olive nucleus, here we investigated interference phenomena of the subthreshold oscillations in the reference system Caenorhabditis elegans for which the structural anatomical connectome was completely known recently. We evaluated how strongly the sinusoidal wave was transmitted between arbitrary two cells in the model network. The region of cell-pairs that are good at transmitting waves changed according to the wavenumber of the wave, for which we named a wavenumber-dependent transmission map. Also, we unraveled that (1) the transmission of all cell-pairs disappeared beyond a threshold wavenumber, (2) long distance and regular patterned transmission existed in the body-wall muscles part of the model network, and (3) major hub cell-pairs of the transmission were identified for many wavenumber conditions. A theoretical and computational model presented in this study provided fundamental insight for understanding how the multi-path constructive/destructive interference of the subthreshold oscillations propagating on electrically coupled neural networks could generate wavenumber-dependent synchronized rhythmic activity. © 2024, Chang et al. 2024-12-31T15:00:00Z