2024
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December 16, 2024 (11:00 – )
Online SemiarDr. Naoto Hori (Nottingham University) -
July 10, 2024 (15:00 – 16:00)
Room 210, 2nd Floor, Main Research BuildingProf. Kenneth M. Merz Jr. (Michigan State University) -
July 10, 2024 (15:00 – 16:00)
Online Semiar“Modeling conformational cycles of ion channels on millisecond scale”
Prof. Erik Lindahl (Stockholm University & KTH) -
May 23, 2024 (11:00 – )
Online Semiar“Modeling conformational cycles of ion channels on millisecond scale”
Dr. Jeremy C Smith (Oak Ridge National Laboratory) -
January 17, 2024 (13:00 – )
Online Seminar（210）“Interactions of Kratom Alkaloids with Membrane Lipid Bilayers”
Dr. Siti Azma (Faculty of Pharmacy, Universiti Teknologi MARA)Prominent alkaloids derived from Mitragyna speciosa exhibit considerable potential for various pharmacological applications. Yet, their molecular interactions with cellular membranes remain poorly understood. In this study, molecular dynamics (MD) simulations were employed to investigate the behavior of three alkaloid compounds (mitragynine, 7-hydroxymitragynine and mitragynine pseudoindoxyl) with lipid bilayers. Several model systems comprising pure and/or mixed alkaloids were embedded in a fully hydrated dipalmitoylphosphatidylcholine (DPPC) lipid bilayer, and simulated using the GROMACS program for a duration of 100-200 ns. The simulation results show the alkaloids diffused into the lipid bilayer region in less than 50 ns duration. We observed the molecules preferentially position themselves beneath the lipid head groups. Hydrogen bonds were formed between alkaloids and the carbonyl and phosphate groups of the lipid bilayer, as well as water molecules from the aqueous region. These findings highlight the hydrophobic nature of the alkaloids, facilitating their integration into lipid bilayers. This study contributes valuable insights for the development of therapeutic strategies targeting membrane-associated processes.
2023
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December 25, 2023 (13:30 – )
Room 210, 2nd Floor, Main Research BuildingProf. Wonpil Im (Lehigh university) -
June 6, 2023 (16:00 – 17:00)
Room 210, 2nd Floor, Main Research Building“(Hopefully Kind) Guide to Quantum Computing for Computational Molecular/Material Scientists”
Prof. Wataru Mizukami (Osaka University)Quantum computing has been advancing rapidly since around 2014, and in Japan, RIKEN launched its cloud-based quantum computer in the cloud in March this year. While current quantum computers are not yet practical for real-world challenges, the development of algorithms for them is thriving. In this seminar, which is aimed primarily at computational molecular/material scientists, I will give a brief overview of quantum computing complemented by hands-on demonstrations and discuss its current status. -
April 27, 2023 (15:00 – 16:00)
Room 210, 2nd Floor, Main Research Building“Molecular Theories for Chemical Condensed Phase”
Prof. Hirofumi Sato (Department of Engineering, Kyoto University) -
March 13, 2023 (16:00 – )
Online seminar“Collagen: a biological rubber band or a mega-enzyme?”
Prof. Frauke Greater (Heidelberg Institute for Theoretical Studies) -
March 3, 2023 (13:00 – )Dr. Benedikt Rennekamp amd Dr. Matthias Brosz
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January 27, 2023 (15:00 – )
Room 210, 2nd Floor, Main Research Building“Elucidation of Cataytic Mechanisms for Nitric Oxide Reductases by Time-resolved Techniques “
Dr. Takehiko Tosha (RIKEN SPring-8 center)Nitric oxide (NO) plays diverse and pivotal roles in various biological processes although NO shows high cytotoxicity. In microbial denitrification process, a form of anaerobic respiration, in which nitrate or nitrite is reduced to dinitrogen in a step-wise manner, NO is produced as an intermediate product. To eliminate the cytotoxic effect of NO, microorganisms utilize NO reductase (NOR), which decomposes two NO molecules to nitrous oxide (N2O) using two protons and electrons (2NO + 2H+ + 2e- → N2O + H2O). There are two types of NORs in microbial denitrification; one is soluble NOR (P450nor) observed in fungi and the other is bacterial membrane-integrated NOR (cNOR). Although the extensive efforts for understanding the mechanisms for NO reduction by NORs, the reaction mechanisms are still in debate mainly due to the limited information on the short-lived reaction intermediates. In this study, we utilized caged NO (BNN5), which releases NO within micro-second time domain upon UV illumination, as a trigger for the NOR reaction, and applied it for time-resolved spectroscopic and structural analyses for the reaction intermediates. The time-resolved techniques combined with caged NO provided invaluable information on the reaction mechanisms both in P450nor and cNOR. 1) P450nor. P450nor catalyzes NO reduction at a thiolate-coordinated heme active center. The resting ferric enzyme reacts with one NO molecule to form ferric NO-bound species, followed by a hydride transfer from NADH to produce a short-lived reaction intermediate called intermediate I [1]. Then, intermediate I reacts with second NO molecule to produce N2O. Because the structural characterization of intermediate I is a key to understand the reaction mechanism in P450nor, we aimed to determine the atomic and electronic structures of intermediate I. The time-resolved X-ray crystallography using X-ray free electron laser (XFEL) and caged NO gave the molecular structure of intermediate I [2-3]. In addition, the time-resolved IR analysis showed that the N-O stretching frequency (nNO) of intermediate I was detected at 1290 cm-1 [3]. Using these structural information, we can conclude that intermediate I is a Fe3+-NHO●- species. Thus, NO reduction by P450nor proceeds via radical coupling reaction. 2) cNOR. The active site of cNOR consists of heme and non-heme iron (FeB). Since the NO reduction reaction by cNOR is finished within milli-second time domain, the reaction intermediates were poorly understood. The time-resolved visible absorption measurement using caged NO showed that the fully reduced cNOR produced N2O via three steps [4]. In the 1st step, one NO molecule binds to reduced cNOR to form a NO-bound species in ~5 ms. The NO-bound species is converted to another chemical species without protonation and second NO binding at ~100 ms (2nd step). Finally, the second NO biding and the protonation to the reaction intermediate yield N2O in the milli-second 3rd step. To get further insights into the structure of the intermediates, we aimed to trap the reaction intermediates by the photolysis of caged NO under cryogenic temperature (cryo-photolysis) and following thermal annealing. The cryo-photolysis of caged NO and subsequent annealing at ~160 K for cNOR produced a species showing g = ~4 signal in EPR spectroscopy. Taken together with the fact that the nNO was detected at 1683 cm-1 by the TR-IR measurement at 5 ms, intermediate 1 is a non-heme Fe-NO species [5]. These findings allow us to propose a revised mechanism for the NO reduction reaction by cNOR. References [1] Shiro et al. J. Biol. Chem. 270, 1617-1623 (1995). [2] Tosha et al. Nat. Commun. 8, 1584 (2017). [3] Nomura et al. Proc. Natl. Acad. Sci. USA, 118, e2101481118 (2021). [4] Takeda et al. Bull. Chem. Soc. Jpn. 93, 825-833 (2020). [5] Takeda et al. J. Phys. Chem. B, in press.
2022
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November 4, 2022 (10:00 – )
Room 210, 2nd Floor, Main Research Building“Accurate modeling of the electrostatic potential maps of proteins”
Dr. Marta Kulik (University of Warsaw, Poland)The quality of image and diffraction data from cryo-electron microscopy and micro-electron diffraction is rapidly increasing. At the same time, the approaches to model the electrostatic potential maps of macromolecular systems containing proteins have significantly improved and reach beyond the simple point charges or spherical independent atom model (IAM). We recently applied the multipolar electron scattering factors to calculate the theoretical potential for proteins [1], without reaching the expensive quantum calculations. We have used the transferable aspherical atom model (TAAM) with the Multipolar Atom Types from Theory and Statistical clustering (MATTS) data bank (successor of UBDB2018 [2]). This data bank gathers aspherical atom types, useful for deriving the multipolar electron scattering factors. MATTS is a database universal for proteins, RNA, and other macromolecules as the atom types are transferable between similar chemical environments. Using MATTS it is possible to recreate the electron density distribution of macromolecules via structure factors [3] or to calculate the accurate electrostatic potential maps for small molecules [4]. MATTS is able to reproduce the molecular electrostatic potential of molecules within their entire volume better than the simple point charge models used in molecular mechanics or neutral spherical models used in electron crystallography. [1] M. Kulik, M. L. Chodkiewicz, P. M. Dominiak, Acta Cryst. D, 2022, 78 [2] Kumar et al., Acta Cryst. A 2019, 75, 398-408 [3] Chodkiewicz et al., J. Appl. Cryst. 2018, 51, 193-199 [4] Gruza et al., Acta Cryst. A 2020, 76, 92-109 -
November 4, 2022 (10:00 – )
Room 210, 2nd Floor, Main Research Building“The case of an aminoglycoside-sensing riboswitch”
Dr. Piotr Chyży (Biomolecular Machines Laboratory, Centre of New Technologies University of Warsaw, Poland)We know a wide range of mechanisms that regulate gene expression in cells. Usually, they are based on modulating crucial steps of transcription, but they can also stall translation in the cytoplasm. In bacteria hindering translation often occurs with the help of RNA aptamers that specifically bind ligands initiating a biological response. One such RNA aptamer is a synthetic N1 riboswitch that binds aminoglycoside antibiotics. When we incorporate N1 riboswitch into cellular mRNA, its secondary structure regulates the aminoglycoside-dependent accessibility of ribosomes to the transcript. Suppose we design such controllable RNA fragments in a ligand-dependent manner, we could use them as molecular targets for antimicrobial compounds. However, before we even start designing RNA aptamers for any therapeutic use, we need to understand their mode of action. Thus, we focused on the smallest synthetic RNA aptamer found active in vivo – N1 riboswitch. To understand the functioning of this RNA aptamer, we characterized its molecular recognition by various aminoglycosides. Next, we explained how single-point mutations change its regulatory properties and how they affect the ligand association process. To achieve this aim, we performed replica-exchange molecular dynamics simulations to enhance the sampling of the conformational space. As a result, we explained why paromomycin is the only inactive antibiotic and how the A17G mutant reduces the ligand binding affinity. We also successfully made the first attempt to implement the multi-dimensional simulations of a system containing a ligand-nucleic acid complex to characterize the association process. The obtained association and binding paths for neomycin corroborate with experimental data and suggest a two-step binding mode. -
October 28, 2022 (16:00 – 17:00)
Room 210, 2nd Floor, Main Research Building“Overtone and combination vibrational transitions in bacteriorhodopsin: from the retinal to internal water molecules.”
Prof. Victor Lorenz-Fonfria (Membrane Biophysics Group, Institute of Molecular Science, Universitat de València, Spain)Rhodopsins are light-sensitive membrane proteins harvesting a retinal chromophore, working either as proton/ion pumps, receptors, or proton/ion channels. Among them, the light-driven proton-pump bacteriorhodopsin is the most studied and best understood. Although many experiments and simulations have contributed to our current understanding of how BR pumps protons, vibrational spectroscopies (mostly resonance Raman and IR difference spectroscopy) have played a central role in many conceptual advances. Many of these studies have addressed vibrations localized either in the retinal, in carboxylic side chains or in internal water molecule, as well as how these change along different intermediate states (K, L, M, N and O) populated along the proton-pumping mechanism before recovering the initial and resting state BR. Virtually all vibrational studies on BR or other rhodopsins have focused on fundamental transitions, from the vibrational ground state to the first excited state. In this presentation I will first talk about newly reported bands between 2600-1900 cm-1 in the K-BR difference spectrum at 77K. We tentatively assigned them to overtone and combination bands from C-C stretches and hydrogen-out-of-plane (HOOP) vibrations of the retinal in the BR and K states. For the BR state, we have supported these assignments with anharmonic vibrational calculations. I will explain how comparing bands from overtones/combination transitions with bands from fundamental transitions we draw some interesting conclusions about mechanical and electronic anharmonicities in the C-C stretches and HOOP vibrations of the retinal [1]. In addition, I will present preliminary results showing changes in the overtone bands of the retinal in the BR state with temperature, pointing to changes in the all-trans retinal conformation as temperature goes below 170 K , changes silent in fundamental bands. This result highlights a potentially higher sensitivity of overtones transitions to conformation than for fundamental transitions, at least for retinal C-C stretches. We have also explored the region between 7000-4000 cm-1, part of the near IR region that is still accessible to FTIR spectrometers. I will present and discuss the detection of overtone transitions of O-H (O-D) vibrations from internal water molecules in the M-BR difference spectrum at room-temperature. These vibrations include the dangling O-H (O-D) stretch of water 401, part of the pentagonal cluster in the BR state, and the dangling O-H (O-D) stretch of a water molecule, part of a putatively water wire formed in the M intermediate between Asp96 and the retinal Schiff base. -
September 16, 2022 (13:30 – 15:00)
Room 210, 2nd Floor, Main Research Building“Protein Structure Modeling and Quality Evaluation from Cryo-EM maps Using DAQ Score”
Dr. Genki Terashi (Kihara Bioinformatics Laboratory, Purdue University, U.S.A)