A5061267883- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Mass Spectrometry Techniques and Applications
- Endoplasmic Reticulum Stress and Disease
- Bacterial Genetics and Biotechnology
- Pancreatic function and diabetes
- Epigenetics and DNA Methylation
- Spectroscopy and Quantum Chemical Studies
- Cellular transport and secretion
- RNA modifications and cancer
- Folate and B Vitamins Research
- Enzyme Structure and Function
- Genetics and Neurodevelopmental Disorders
- Microbial Metabolic Engineering and Bioproduction
- Genomics and Chromatin Dynamics
- Gene Regulatory Network Analysis
- Microtubule and mitosis dynamics
- Cancer-related gene regulation
University of Tsukuba
2020-2024
Abstract Hevin is a secreted extracellular matrix protein that encoded by the SPARCL1 gene. Recent studies have shown plays an important role in regulating synaptogenesis and synaptic plasticity. Mutations gene increase risk of autism spectrum disorder (ASD). However, molecular basis how mutations ASD not been fully understood. In this study, we show one associated with impairs normal secretion. We identified mutants lacking EF-hand motif through analyzing ASD-related mice vulnerable...
Molecular dynamics (MD) simulation has become a powerful tool because it provides time series of protein at high temporal-spatial resolution. However, the accessible timescales MD are shorter than those biologically rare events. Generally, long-time simulations over microseconds required to detect Therefore, is desirable develop rare-event-sampling methods. For method, we have developed parallel cascade selection (PaCS-MD). PaCS-MD generates transition pathways from given source structure...
Protein conformations in cells are not solely determined by amino acid sequences; they also depend on cellular environments. For instance, the ribosome tunnel induces its specific α-helix formation during cotranslational folding. Owing to link between these temporally and biological functions, mechanism of inside has been previously explored. Consequently, conformational restrictions were considered one driving forces formation. Conversely, ribosomal environment, including chemical...
Understanding the influence of cellular environment on protein conformations is crucial for elucidating functions within living cells. In studies using molecular dynamics (MD) simulation, carbon nanotubes and hydrophobic cages have been widely used to emulate inside specific large biomolecules such as ribosome tunnels chaperones. However, recent suggest that these uniform models may not adequately capture environmental effects each biomolecule. Based facts, it necessary generate spherical...
Enzymatic activity is regulated by various mechanisms to ensure biologically proper functions. Notable instances of such regulation in homodimeric enzymes include "all-of-the-sites activity" and "half-of-the-sites activity". The difference these activities lies whether one or both the subunits are simultaneously active. Owing its uniqueness, mechanism half-of-the-sites has been widely investigated. Consequently, structural asymmetry derived from cooperative motion considered induce activity....
Abstract Trp-cage is an artificial 20-residue protein and forms a hydrophobic core at its central cage upon folding. In the present study, folding of was addressed by parallel cascade selection molecular dynamics (PaCS-MD). Our results PaCS-MD indicate that flip side chain tryptophan (W6) correlated with overall conclusion, stochastic W6 regulates into native or mis-folded states Trp-cage.
Biological functions are related to long-time protein dynamics (rare events) that induced over microseconds. Such can be investigated using molecular (MD) simulations. However, the detection of rare events remains challenging conventional MD (cMD) since accessible timescales cMD shorter than those biological functions. Recently, parallel cascade selection (PaCS-MD) has been proposed detect such events, wherein transition paths generated between a given reactant and product. As an extension,...
Free energy landscapes (FELs) of proteins are indispensable for evaluating thermodynamic properties. Molecular dynamics (MD) simulation is a computational method calculating FELs; however, conventional MD frequently fails to search broad conformational subspace due its accessible timescale, which results in the calculation an unreliable FEL. To subspace, external bias can be imposed on protein system, and biased sampling tends cause strong perturbation that might collapse structures,...
DNA methyl transferase1 (Dnmt1) preferentially methylates hemi-methylated DNA. Upon the methylation of DNA, a group is provided by S-adenosyl-l-methionine (SAM), which becomes product S-adenosyl-l-homocysteine (SAH). We performed molecular dynamics (MD) simulations to trace SAM and address SAH in inactivated Dnmt1 mice. Our MD found that was more stable than under environment, indicating an exchange cofactors might occur inactivation state before next process. enzyme A showed Dnmt1, have occurred
Abstract Hevin is a secreted extracellular matrix protein that encoded by SPARCL1 gene. Recent studies show plays an important role in regulating synaptogenesis and synaptic plasticity. Mutations gene increase the risk of autism spectrum disorder (ASD). However, molecular basis how mutations ASD has not been fully understood. In this study, we one associated with impairs normal secretion. We identified mutants lacking EF-hand motif through analyzing ASD-related mice vulnerable spliceosome...
Since proteins perform biological functions through their dynamic properties, molecular dynamics (MD) simulation is a sophisticated strategy for investigating functions. Analyses of trajectories provide statistical information about specific protein as free-energy landscape (FEL). However, the timescale normal MD shorter than that functions, resulting in statistically insufficient conformational sampling, finally leading to unreliable FEL calculation. To search broad configurational...