Biology subjects

Choi, M.-k.

Publications and source records attributed to Choi, M.-k..

4 recordsLinked to original sources

bioRxiv2024

An accelerated molecular dynamics study for investigating protein pathways using the bond-boost hyperdynamics method

Molecular dynamics (MD) simulation is an important tool for understanding protein dynamics and the thermodynamic properties of proteins. However, due to the high computational cost of MD simulations, it is still challenging to explore a wide conformational space. To solve this problem, a variety of accelerated MD schemes have been proposed over the past few decades. The bond-boost method (BBM) is one of such accelerated MD schemes, which expedites escape events from energy basins by adding a bias potential based on changes in bond length. In this paper, we present a new methodology based on the BBM for accelerating the conformational transition of proteins. In our modified BBM, the bias potential is constructed using the dihedral angle and hydrogen bond, which are more suitable variables to monitor the conformational change in proteins. Additionally, we have developed an efficient algorithm compatible with the LAMMPS package. The method is validated with the conformational change of Adenylate kinase (AdK) by comparing the conventional and accelerated MD simulation results. Based on the accelerated MD results, the characteristics of AdK are investigated by monitoring the conformational transition pathways and the behavior of interdomain salt bridges. Moreover, the free energy landscape calculated using umbrella sampling confirms all the states identified by the accelerated MD simulation are the free energy minima and the system makes transitions following the path indicated by the free energy landscape. Our efficient approach is expected to play a key role in investigating transition pathways in a wide range of protein simulations.

biophysics↗

bioRxiv2024

Structural diversity of mitochondria in the neuromuscular system across development

As an animal matures, its neural circuit undergoes alterations, yet the developmental changes in intracellular organelles to facilitate these changes is less understood. Using 3D electron microscopy and deep learning, we developed semi-automated methods for reconstructing mitochondria in C. elegans and collected mitochondria reconstructions from normal reproductive stages and dauer, enabling comparative study on mitochondria structure within the neuromuscular system. We found that various mitochondria structural properties in neurons correlate with synaptic connections and these properties are preserved across development in different neural circuits. To test the necessity of these universal mitochondria properties, we examined the behavior in drp-1 mutants with impaired mitochondria fission and discovered that it caused behavioral deficits. Moreover, we observed that dauer neurons display distinctive mitochondrial features, and mitochondria in dauer muscles exhibit unique reticulum-like structure. We propose that this specialized mitochondria structure may serve as an adaptive mechanism to support stage-specific behavioral and physiological needs.

neuroscience↗

bioRxiv2023

Mind of a dauer: Comparative connectomics reveals developmental plasticity

A fundamental question in neurodevelopmental biology is how flexibly the nervous system changes during development. To address this, we reconstructed the complete connectome of dauer, an alternative developmental stage of nematodes with distinct behavioral characteristics, by volumetric reconstruction and automated synapse detection using deep learning. With the basic architecture of the nervous system preserved, structural changes in neurons, large or small, were closely associated with connectivity changes, which in turn evoked dauer-specific behaviors such as nictation. Graph theoretical analyses revealed significant dauer-specific rewiring of sensory neuron connectivity and increased clustering within motor neurons in the dauer connectome. We suggest that the nervous system in the nematode, probably animals in general, has evolved to respond to harsh environments by reversibly developing a quantitatively and qualitatively differentiated connectome.

neuroscience↗

bioRxiv2022

dach-1, a cytochrome P450 gene, regulates synaptic and developmental plasticity during the diapause of Caenorhabditis elegans

Animals exhibit phenotypic plasticity through the interaction of genes with the environment, and little is known about the genetic factors that change synaptic function at different developmental stages. Here, we investigated the genetic determinants of how developmental stages alter synaptic transmission using the free-living nematode Caenorhabditis elegans. C. elegans enters the stress-resistant dauer larval stage under harsh conditions. Although dauer is known to have reduced permeability and increased resistance to most known exogenous chemicals, we discovered that dauer is hypersensitive to a cholinesterase inhibitor, aldicarb. To investigate genes regulating dauer-specific acetylcholine transduction, we first screened for aldicarb-resistant mutations in dauer and then performed a secondary screen to rule out aldicarb-resistant mutations that also affect adults. We isolated two different mutations of a single gene called cyp-34A4 or dach-1 encoding a cytochrome P450. In the non-dauer stages, dach-1 is mainly expressed in the intestine, but its expression is robustly increased in the epidermis of dauers. By tissue-specific rescue experiments, we found that dach-1 modulates aldicarb sensitivity in a cell non-autonomous manner. In addition, dach-1 plays pleiotropic functions in dauers by regulating quiescence and surviving heat shock and hyperosmolar stress. Our study reveals novel functions of the cytochrome P450 in synaptic and physiological changes during developmental plasticity.

genetics↗