Editorial

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3 pages, 181 KiB

Open AccessEditorial

Molecular Dynamics—From Macromolecule to Small Molecules

by Ki Hyun Nam

Int. J. Mol. Sci. 2022, 23(10), 5676; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105676 - 19 May 2022

Cited by 1 | Viewed by 1170

Abstract

All natural molecules have their own physical, chemical, or biological properties and functions [...] Full article

(This article belongs to the Special Issue Molecular Dynamics from Macromolecule to Small Molecules)

5 pages, 391 KiB

Open AccessEditorial

Molecular Dynamics—From Small Molecules to Macromolecules

by Ki Hyun Nam

Int. J. Mol. Sci. 2021, 22(7), 3761; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073761 - 05 Apr 2021

Cited by 17 | Viewed by 3703

Abstract

All molecular systems, from small molecules to macromolecules, exhibit specific characteristics for a specific environment and time. In order to gain an accurate understanding of the functions of all types of molecules, studies of their structure and dynamics are essential. Through dynamic studies, [...] Read more.

All molecular systems, from small molecules to macromolecules, exhibit specific characteristics for a specific environment and time. In order to gain an accurate understanding of the functions of all types of molecules, studies of their structure and dynamics are essential. Through dynamic studies, using techniques such as spectroscopy, structure determination, and computer analysis, it is possible to collect functional information on molecules at specific times and in specific environments. Such information not only reveals the properties and mechanisms of action of molecules but also provides insights that can be applied to various industries, such as the development of new materials and drugs. Herein, I discuss the importance of molecular dynamics studies, present the time scale of molecular motion, and review techniques for analyzing molecular dynamics. Full article

(This article belongs to the Special Issue Molecular Dynamics from Macromolecule to Small Molecules)

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Research

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18 pages, 4777 KiB

Open AccessArticle

Conformational Dynamics of the Soluble and Membrane-Bound Forms of Interleukin-1 Receptor Type-1: Insights into Linker Flexibility and Domain Orientation

by João P. Luís, Ana I. Mata, Carlos J. V. Simões and Rui M. M. Brito

Int. J. Mol. Sci. 2022, 23(5), 2599; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052599 - 26 Feb 2022

Cited by 2 | Viewed by 2310

Abstract

Interleukin-1 receptor type 1 (IL-1R1) is a key player in inflammation and immune responses. This receptor regulates IL-1 activity in two forms: as a membrane-bound form and as a soluble ectodomain. The details and differences between the conformational dynamics of the membrane-bound and [...] Read more.

Interleukin-1 receptor type 1 (IL-1R1) is a key player in inflammation and immune responses. This receptor regulates IL-1 activity in two forms: as a membrane-bound form and as a soluble ectodomain. The details and differences between the conformational dynamics of the membrane-bound and the soluble IL-1R1 ectodomains (ECDs) remain largely elusive. Here, we study and compare the structural dynamics of the soluble and membrane-bound IL-1R1-ECDs using molecular dynamics (MD) simulations, focusing on the flexible interdomain linker of the ECD, as well as the spatial rearrangements between the Ig-like domains of the ECD. To explore the membrane-bound conformations, a full-length IL-1R1 structural model was developed and subjected to classical equilibrium MD. Comparative analysis of multiple MD trajectories of the soluble and the membrane-bound IL-1R1-ECDs reveals that (i) as somewhat expected, the extent of the visited “open-to-closed” transitional states differs significantly between the soluble and membrane-bound forms; (ii) the soluble form presents open-closed transitions, sampling a wider rotational motion between the Ig-like domains of the ECD, visiting closed and “twisted” conformations in higher extent, whereas the membrane-bound form is characterized by more conformationally restricted states; (iii) interestingly, the backbone dihedral angles of residues Glu202, Glu203 and Asn204, located in the flexible linker, display the highest variations during the transition between discrete conformational states detected in IL-1R1, thus appearing to work as the “central wheel of a clock’s movement”. The simulations and analyses presented in this contribution offer a deeper insight into the structure and dynamics of IL-1R1, which may be explored in a drug discovery setting. Full article

(This article belongs to the Special Issue Molecular Dynamics from Macromolecule to Small Molecules)

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10 pages, 2021 KiB

Open AccessArticle

Anti-Kasha Behavior of 3-Hydroxyflavone and Its Derivatives

by Ka Wa Fan, Hoi Ling Luk and David Lee Phillips

Int. J. Mol. Sci. 2021, 22(20), 11103; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222011103 - 14 Oct 2021

Cited by 6 | Viewed by 1628

Abstract

Excited state intramolecular proton transfer (ESIPT) in 3-hydroxyflavone (3HF) has been known for its dependence on excitation wavelength. Such a behavior violates Kasha’s rule, which states that the emission and photochemistry of a compound would only take place from its lowest excited state. [...] Read more.

Excited state intramolecular proton transfer (ESIPT) in 3-hydroxyflavone (3HF) has been known for its dependence on excitation wavelength. Such a behavior violates Kasha’s rule, which states that the emission and photochemistry of a compound would only take place from its lowest excited state. The photochemistry of 3HF was studied using femtosecond transient absorption spectroscopy at a shorter wavelength excitation (266 nm), and these new experimental findings were interpreted with the aid of computational studies. These new results were compared with those from previous studies that were obtained with a longer wavelength excitation and show that there exists a pathway of proton transfer that bypasses the normal first excited state from the higher excited state to the tautomer from first excited state. The experimental data correlate with the electron density difference calculations such that the proton transfer process is faster on the longer excitation wavelength than compared to the shorter excitation wavelength. Full article

(This article belongs to the Special Issue Molecular Dynamics from Macromolecule to Small Molecules)

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19 pages, 3283 KiB

Open AccessArticle

Structural Dynamics of C₂F₄I₂ in Cyclohexane Studied via Time-Resolved X-ray Liquidography

by Jain Gu, Seonggon Lee, Seunghwan Eom, Hosung Ki, Eun Hyuk Choi, Yunbeom Lee, Shunsuke Nozawa, Shin-ichi Adachi, Jeongho Kim and Hyotcherl Ihee

Int. J. Mol. Sci. 2021, 22(18), 9793; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22189793 - 10 Sep 2021

Cited by 4 | Viewed by 2159

Abstract

The halogen elimination of 1,2-diiodoethane (C₂H₄I₂) and 1,2-diiodotetrafluoroethane (C₂F₄I₂) serves as a model reaction for investigating the influence of fluorination on reaction dynamics and solute–solvent interactions in solution-phase reactions. While the [...] Read more.

The halogen elimination of 1,2-diiodoethane (C₂H₄I₂) and 1,2-diiodotetrafluoroethane (C₂F₄I₂) serves as a model reaction for investigating the influence of fluorination on reaction dynamics and solute–solvent interactions in solution-phase reactions. While the kinetics and reaction pathways of the halogen elimination reaction of C₂H₄I₂ were reported to vary substantially depending on the solvent, the solvent effects on the photodissociation of C₂F₄I₂ remain to be explored, as its reaction dynamics have only been studied in methanol. Here, to investigate the solvent dependence, we conducted a time-resolved X-ray liquidography (TRXL) experiment on C₂F₄I₂ in cyclohexane. The data revealed that (ⅰ) the solvent dependence of the photoreaction of C₂F₄I₂ is not as strong as that observed for C₂H₄I₂, and (ⅱ) the nongeminate recombination leading to the formation of I₂ is slower in cyclohexane than in methanol. We also show that the molecular structures of the relevant species determined from the structural analysis of TRXL data provide an excellent benchmark for DFT calculations, especially for investigating the relevance of exchange-correlation functionals used for the structural optimization of haloalkanes. This study demonstrates that TRXL is a powerful technique to study solvent dependence in the solution phase. Full article

(This article belongs to the Special Issue Molecular Dynamics from Macromolecule to Small Molecules)

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23 pages, 7445 KiB

Open AccessArticle

Tunneling Quantum Dynamics in Ammonia

by Ciann-Dong Yang and Shiang-Yi Han

Int. J. Mol. Sci. 2021, 22(15), 8282; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22158282 - 31 Jul 2021

Cited by 4 | Viewed by 4909

Abstract

Ammonia is a well-known example of a two-state system and must be described in quantum-mechanical terms. In this article, we will explain the tunneling phenomenon that occurs in ammonia molecules from the perspective of trajectory-based quantum dynamics, rather than the usual quantum probability [...] Read more.

Ammonia is a well-known example of a two-state system and must be described in quantum-mechanical terms. In this article, we will explain the tunneling phenomenon that occurs in ammonia molecules from the perspective of trajectory-based quantum dynamics, rather than the usual quantum probability perspective. The tunneling of the nitrogen atom through the potential barrier in ammonia is not merely a probability problem; there are underlying reasons and mechanisms explaining why and how the tunneling in ammonia can happen. Under the framework of quantum Hamilton mechanics, the tunneling motion of the nitrogen atom in ammonia can be described deterministically in terms of the quantum trajectories of the nitrogen atom and the quantum forces applied. The vibrations of the nitrogen atom about its two equilibrium positions are analyzed in terms of its quantum trajectories, which are solved from the Hamilton equations of motion. The vibration periods are then computed by the quantum trajectories and compared with the experimental measurements. Full article

(This article belongs to the Special Issue Molecular Dynamics from Macromolecule to Small Molecules)

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14 pages, 4545 KiB

Open AccessArticle

Room-Temperature Structure of Xylitol-Bound Glucose Isomerase by Serial Crystallography: Xylitol Binding in the M1 Site Induces Release of Metal Bound in the M2 Site

by Ki Hyun Nam

Int. J. Mol. Sci. 2021, 22(8), 3892; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22083892 - 09 Apr 2021

Cited by 18 | Viewed by 1851

Abstract

Glucose isomerase (GI) is an important enzyme that is widely used in industrial applications, such as in the production of high-fructose corn syrup or bioethanol. Studying inhibitor effects on GI is important to deciphering GI-specific molecular functions, as well as potential industrial applications. [...] Read more.

Glucose isomerase (GI) is an important enzyme that is widely used in industrial applications, such as in the production of high-fructose corn syrup or bioethanol. Studying inhibitor effects on GI is important to deciphering GI-specific molecular functions, as well as potential industrial applications. Analysis of the existing xylitol-bound GI structure revealed low metal occupancy at the M2 site; however, it remains unknown why this phenomenon occurs. This study reports the room-temperature structures of native and xylitol-bound GI from Streptomyces rubiginosus (SruGI) determined by serial millisecond crystallography. The M1 site of native SruGI exhibits distorted octahedral coordination; however, xylitol binding results in the M1 site exhibit geometrically stable octahedral coordination. This change results in the rearrangement of metal-binding residues for the M1 and M2 sites, the latter of which previously displayed distorted metal coordination, resulting in unstable coordination of Mg²⁺ at the M2 site and possibly explaining the inducement of low metal-binding affinity. These results enhance the understanding of the configuration of the xylitol-bound state of SruGI and provide insights into its future industrial application. Full article

(This article belongs to the Special Issue Molecular Dynamics from Macromolecule to Small Molecules)

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16 pages, 2935 KiB

Open AccessArticle

Unfolding and Aggregation of Lysozyme under the Combined Action of Dithiothreitol and Guanidine Hydrochloride: Optical Studies

by Ruslan M. Sarimov, Vladimir N. Binhi, Tatiana A. Matveeva, Nikita V. Penkov and Sergey V. Gudkov

Int. J. Mol. Sci. 2021, 22(5), 2710; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052710 - 08 Mar 2021

Cited by 15 | Viewed by 2833

Abstract

Using a number of optical techniques (interferometry, dynamic light scattering, and spectroscopy), denaturation of hen egg white lysozyme (HEWL) by treatment with a combination of dithiothreitol (DTT) and guanidine hydrochloride (GdnHCl) has been investigated. The denaturing solutions were selected so that protein denaturation [...] Read more.

Using a number of optical techniques (interferometry, dynamic light scattering, and spectroscopy), denaturation of hen egg white lysozyme (HEWL) by treatment with a combination of dithiothreitol (DTT) and guanidine hydrochloride (GdnHCl) has been investigated. The denaturing solutions were selected so that protein denaturation occurred with aggregation (Tris-HCl pH = 8.0, 50 mM, DTT 30 mM) or without aggregation (Tris-HCl pH = 8.0, 50 mM, DTT 30 mM, GdnHCl 6 M) and can be evaluated after 60 min of treatment. It has been found that denatured by solution with 6 M GdnHCl lysozyme completely loses its enzymatic activity after 30 min and the size of the protein molecule increases by 1.5 times, from 3.8 nm to 5.7 nm. Denaturation without of GdnHCl led to aggregation with preserving about 50% of its enzymatic activity. Denaturation of HEWL was examined using interferometry. Previously, it has been shown that protein denaturation that occurs without subsequent aggregation leads to an increase in the refractive index (Δn ~ 4.5 × 10⁻⁵). This is most likely due to variations in the HEWL–solvent interface area. By applying modern optical techniques conjointly, it has been possible to obtain information on the nature of time-dependent changes that occur inside a protein and its hydration shell as it undergoes denaturation. Full article

(This article belongs to the Special Issue Molecular Dynamics from Macromolecule to Small Molecules)

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11 pages, 2112 KiB

Open AccessArticle

Lard Injection Matrix for Serial Crystallography

by Ki Hyun Nam

Int. J. Mol. Sci. 2020, 21(17), 5977; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21175977 - 19 Aug 2020

Cited by 23 | Viewed by 3346

Abstract

Serial crystallography (SX) using X-ray free electron laser or synchrotron X-ray allows for the determination of structures, at room temperature, with reduced radiation damage. Moreover, it allows for the study of structural dynamics of macromolecules using a time-resolved pump-probe, as well as mix-and-inject [...] Read more.

Serial crystallography (SX) using X-ray free electron laser or synchrotron X-ray allows for the determination of structures, at room temperature, with reduced radiation damage. Moreover, it allows for the study of structural dynamics of macromolecules using a time-resolved pump-probe, as well as mix-and-inject experiments. Delivering a crystal sample using a viscous medium decreases sample consumption by lowering the flow rate while being extruded from the injector or syringe as compared to a liquid jet injector. Since the environment of crystal samples varies, continuous development of the delivery medium is important for extended SX applications. Herein, I report the preparation and characterization of a lard-based sample delivery medium for SX. This material was obtained using heat treatment, and then the soluble impurities were removed through phase separation. The lard injection medium was highly stable and could be injected via a syringe needle extruded at room temperature with a flow rate < 200 nL/min. Serial millisecond crystallography experiments were performed using lard, and the room temperature structures of lysozyme and glucose isomerase embedded in lard at 1.75 and 1.80 Å, respectively, were determined. The lard medium showed X-ray background scattering similar or relatively lower than shortenings and lipidic cubic phase; therefore, it can be used as sample delivery medium in SX experiments. Full article

(This article belongs to the Special Issue Molecular Dynamics from Macromolecule to Small Molecules)

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