Journal of Molecular Recognition最新文献

The binding of drugs to plasma proteins determines its fate within the physiological system, hence profound understanding of its interaction within the bloodstream is important to understand its pharmacodynamics and pharmacokinetics and thereby its therapeutic potential. In this regard, our work delineates the mechanism of interaction of Selumetinib (SEL), a potent anti-cancer drug showing excellent effect against multiple solid tumors, with plasma protein bovine serum albumin (BSA), using methods such as absorption, steady-state fluorescence, time-resolved, fluorescence resonance energy transfer, Fourier transform infrared spectra (FTIR), circular dichroism (CD), synchronous and 3D-fluorescence, salt fluorescence, molecular docking and molecular dynamic simulations. The BSA fluorescence intensity was quenched with increasing concentration of SEL which indicates interactions of SEL with BSA. Stern–Volmer quenching analysis and lifetime studies indicate the involvement of dynamic quenching. However, some contributions from the static quenching mechanism could not be ruled out unambiguously. The association constant was found to be 5.34 × 10⁵ M⁻¹ and it has a single binding site. The Förster distance (r) indicated probable energy transmission between the BSA and SEL. The positive entropy changes and enthalpy change indicate that the main interacting forces are hydrophobic forces, also evidenced by the results of molecular modeling studies. Conformation change in protein framework was revealed from FTIR, synchronous and 3D fluorescence and CD studies. Competitive binding experiments as well as docking studies suggest that SEL attaches itself to site I (subdomain IIA) of BSA where warfarin binds. Molecular dynamic simulations indicate the stability of the SEL–BSA complex. The association energy between BSA and SEL is affected in the presence of different metals differently.

Glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) are pentose phosphate pathway enzymes. Compounds with a heterocyclic pyrrole ring system containing this atom can be derivatized with various functional groups into highly effective bioactive agents. In this study, pyrrole derivatives on these enzyme's activity were investigated. The IC₅₀ values of different concentrations of pyrrole derivatives for G6PD were found in the range of 0.022–0.221 mM K_i values 0.021 ± 0.003–0.177 ± 0.021 and for 6PGD IC₅₀ values 0.020–0.147, mM K_i values 0.013 ± 0.002–0.113 ± 0.030 mM. The 2-acetyl-1-methylpyrrole (1g) showed the best inhibition value for G6PD and 6PGD enzymes. In addition, in silico molecular docking experiments were performed to elucidate how these pyrrole derivatives (1a–g) interact with the binding sites of the target enzymes. The study's findings on pyrrole derivatives could be used to create innovative therapeutics that could be a treatment for many diseases, especially cancer manifestations.

G-quadruplexes play a pivotal role in regulating various cellular processes, including gene expression and replication, making them essential structures in understanding, and manipulating cellular functions. The development of G-quadruplex ligands holds significant promise in therapeutic and research applications, offering targeted tools to modulate G-quadruplex structures and potentially influence critical biological pathways. An exciting frontier in G-quadruplex research lies in the exploration of anionic ligands, and their profound impact on stabilizing and modulating G-quadruplex DNA. In this study, the interaction of two anionic phthalocyanine compounds (Zinc (II) phthalocyanine 3,4′,4″,4‴-tetrasulfonic acid, tetrasodium salt, ZnAPC; cobalt (II) phthalocyanine 3,4′,4″,4‴-tetrasulfonic acid, tetrasodium salt, CoAPC) and three separate G-quadruplex-forming DNA sequences was investigated. Interactions were carried out by DNA polymerase stop studies along with spectroscopic studies. According to the results of experimental data, it was determined that ZnAPC actively interacts with the G-quadruplex DNA structures. On the other hand, it was thought that the interaction with CoAPC was less and even occurred in simple electrostatic interactions. K_D constants and B_max constants for the interaction with ZnAPC were calculated. The K_D constants for ZnAPC were found to be (1.16 ± 0.07) × 10⁻⁵, (9.75 ± .24) × 10⁻⁶ and (1.00 ± 0.36) × 10⁻⁴ M for AS1411, Vegf, and Tel21, respectively. Accordingly, it was concluded that ZnAPC interacts with G-quadruplex DNA ligands effectively.

At the beginning of 2024, I took over from Marc van Regenmortel as the third Editor-in-Chief of JMR. The journal was established by Irwin Chaiken in 1988 with affiliation to the International Society for Molecular Recognition (ismr.org) and with a strong focus on methods to measure affinity. Presciently, and quite unusually, the journal was founded to focus on a phenomenon—molecular recognition—and it is a phenomenon that is central to biomolecular science. This has enabled the content of the journal to evolve over time as new techniques, ideas, and applications have emerged. In 1999, Marc van Regenmortel became Editor-in-Chief, introduced new types of articles, and broadened the scope of the journal. For example, the series of comprehensive critical reviews on methods, such as surface plasmon resonance, isothermal calorimetry, and molecular docking, were particularly well read. We, the editors and advisory board members, thank him for his vision, inspiration, dedication, and hard work in successfully steering the journal over the last 25 years. He leaves the journal on solid foundations, publishing on a broad range of molecular recognition topics. Marc sought to make the journal, not only THE place to publish high-quality research on molecular recognition but also a venue for discussion on concepts and controversial issues relating to molecular recognition. We will continue to pursue these aims. For this purpose, we are introducing an additional article category called “Perspective” for short articles with commentaries, discussions, or reviews on current topics. The first two Perspectives are on Marc's contributions to science and the scientific community^{1, 2} and highly recommended reading. We will also aim to nurture the broad community of molecular recognition researchers, for example, through awards at conferences and with the establishment of a new Early Career Advisory Board for the journal.

Now is an appropriate time for JMR to enter into its third epoch. The growing prominence of computational science and the dramatic advances in artificial intelligence are changing how research into molecular recognition is done. This is reflected in the appointment of a theoretical and computational scientist at the helm of JMR. Moreover, the panel of Associate Editors includes two theoreticians as well as other scientists who combine computation with their experimental work. We will be looking to see how artificial intelligence and data science complement our existent methodological toolbox to accelerate molecular recognition research and enable the discovery of new molecules, new binding mechanisms, and new conceptual insights. However, in all the excitement over the new possibilities that such approaches bring, it is important to ensure that computational and machine learning tools and techniques are applied rigorously and carefully, with experimental validation whenever possible. Moreover, we expect that AI will be a

Marc van Regenmortel was the Editor-in-Chief of the Journal of Molecular Recognition for the last 25 years. Without attempting to summarize Marc's exceptional career and achievements, we would like to tell the story of the tortuous and contingent path to the unravelling of a key molecular recognition process in antigenicity. Life is indeed full of contingencies and scientific life, full of meetings and random encounters, is prone to contingencies, a key element in discovery and innovation.

Unlike Jean-Luc Pellequer and Eric Westhof,¹ who were colleagues of Marc H.V. van Regenmortel, I have never met him in person. However, I can add my voice to the discussion of how contingency or serendipity has led me to productively collaborate with Marc (unfortunately, exclusively in the on-line format), resulting in the publication of a joint paper in 2020.² Before moving to this part of my story, a short historical excurse is needed.

My first (once again, exclusively virtual) encounter with Marc took place in 2004, when he played a crucial role in our work on one of the first comprehensive reviews on the roles of intrinsically disordered proteins and regions (IDPs/IDRs) in molecular recognition, regulation, and cell signaling.³ In the middle of 2004, I joined the Center for Computational Biology and Bioinformatics (CCBB) at the Indiana University-Purdue University at Indianapolis (IUPUI) that was created and headed by Prof. A. Keith Dunker, whom I worked with for 6 years on different aspects of the protein intrinsic disorder phenomenon. One of my first projects there was analysis of the then-available literature data on the functionality of intrinsic disorder.

By that time, it became clear that although IDPs/IDRs have been mostly ignored by the scientific community since the inception of the lock-and-key model by Hermann Emil Louis Fischer (1852–1919) in 1894,^{4, 5} many aspects of protein functionality could not be explained using this important model and its associated sequence-structure-function paradigm. In fact, many protein functions do not require specific structures, instead relying on conformational flexibility, and as a result, many biologically active proteins (or protein regions) do not have unique structures, instead being intrinsically disordered.^6-15 However, the concept of functional disorder was still met with strong skepticism by the scientific community, especially by those who worked in structural biology.

This brings us to my first example of Marc-centric contingency or serendipity. When Keith contacted Marc to check if the manuscript we were working on would fit the scope of the Journal of Molecular Recognition, to our big surprise, we received very enthusiastic support. Those times were still the early days of protein intrinsic disorder, and many scientific journals were simply dismissing the idea of functional disorder as nonsensical (as an example, it took more than a year to publish my first paper on this subject (Ref. 16), which was rejected by 14 journals before being eventually accepted by Proteins⁷). During the preparation of the manuscript for the Journal of Molecular Recognition, we had a productive exchange with Marc, which was very useful and is reflected in the acknowledgement in the resulting paper that reads “Both A.K.D. and V.N.U. t

Founded in June 2006, after a first seminal French-speaking conference held on the topic “Atelier Nanobiosciences: protéines et membranes” in Nîmes in June 2004, the AFMBioMed Conference brings researchers and students from around the world together to discuss the latest scientific results of atomic force microscopy in life sciences and medicine.^{1, 2} A full account of the AFMBioMed history can be found here.³ AFMBioMed organized its first international meeting in Barcelona, Spain, in spring 2007⁴ and this was followed, at 18-month intervals, by Monterey, CA, USA, in fall 2008,⁵ Crveni otok (Red Island) near the Adriatic City of Rovinj, Croatia, in spring 2010,⁶ Paris in summer 2011,⁷ Shanghai in spring 2013,⁸ San Diego in fall 2014,⁹ Porto in spring 2016,¹⁰ Krakow in fall 2017,³ and Münster in fall 2019.¹¹

Members of the scientific committee for the tenth edition of the AFMBioMed meeting in Nagoya-Okasaki, Japan, in summer 2022 include past and present organizers Takayuki Uchihashi (Nagoya University, Japan), Hermann Schillers (University of Münster, Germany), Malgorzata Lekka (Polish Academy of Sciences, Poland), Susana R. Sousa (i3S|INEB, Porto, Portugal), Adam Engler (UCSD, San Diego, USA), Jun Hu (SINAP, Shanghai, China), Sanjay Kumar (University of California, Berkeley, USA), Daniel Navajas (Universitat de Barcelona, Barcelona, Spain), Simon Scheuring (Institut National de la Santé et de la Recherche Médicale (INSERM) U1006, Marseille, France), Vesna Svetlicic (Rudjer Boskovic Institute, Zagreb, Croatia), the original founders of the conference Pierre Parot (IACA) and Jean-Luc Pellequer (CEA/DRF, Institut de Biologie Structurale, Grenoble, France), as well as the four invited chairs: Alice Pyne (Sheffield University, UK), Felix Rico (Aix-Marseille University—INSERM, France), Takaharu Okajima (Hokkaido University, Japan), and Noriyuki Kodera (Kanazawa University, Japan).

The 10th AFMBioMed was scheduled as a landmark conference. Despite the round number 10, it was the last conference organized with a single AFM sponsor (more below). It should have been the last conference that Pierre Parot, the co-founder of AFMBioMed, would participate in. At the end of the 9th conference in Münster, the 10th AFMBioMed conference was initially planned for spring 2021, the cherry blossom season in Japan. Unfortunately, the COVID-19 pandemic modified our plan. The conference was postponed every 6 months while waiting for the reopening of travel to Japan (as well as other countries). In early 2022, the organi

Although antibodies, a key element of biorecognition, are frequently used as biosensor probes, the use of these large molecules can lead to adverse effects. Fab fragments can be reduced to allow proper antigen-binding orientation via thiol groups containing Fab sites that can directly penetrate Au sites chemically. In this study, the ability of the surface plasmon resonance (SPR) sensor to detect Salmonella was studied. Tris(2-carboxyethyl)phosphine was used as a reducing agent to obtain half antibody fragments. Sensor surface was immobilized with antibody, and bacteria suspensions were injected from low to high concentrations. Response units were changed by binding first reduced antibody fragments, then bacteria. The biosensor was able to determine the bacterial concentrations between 10³ and 10⁸ CFU/mL. Based on these results, the half antibody fragmentation method can be generalized for faster, label-free, sensitive, and selective detection of other bacteria species.

Tetramethrin (TMT) is a commonly used insecticide and has a carcinogenic and neurodegenerative effect on humans. The binding mechanism and toxicological implications of TMT to human serum albumin (HSA) were examined in this study employing a combination of biophysical and computational methods indicating moderate binding affinity and potential hepato and renal toxicity. Fluorescence quenching experiments showed that TMT binds to HSA with a moderate affinity, and the binding process was spontaneous and predominantly enthalpy-driven. Circular dichroism spectroscopy revealed that TMT binding did not induce any significant conformational changes in HSA, resulting in no changes in its alpha-helix content. The binding site and modalities of TMT interactions with HSA as computed by molecular docking and molecular dynamics simulations revealed that it binds to Sudlow site II of HSA via hydrophobic interactions through its dimethylcyclopropane carboxylate methyl propanyl group. The structural dynamics of TMT induce proper fit into the binding site creating increased and stabilizing interactions. Additionally, molecular mechanics–Poisson Boltzmann surface area calculations also indicated that non-polar and van der Waals were found to be the major contributors to the high binding free energy of the complex. Quantum mechanics (QM) revealed the conformational energies of the binding confirmation and the degree of deviation from the global minimum energy conformation of TMT. The results of this study provide a comprehensive understanding of the binding mechanism of TMT with HSA, which is important for evaluating the toxicity of this insecticide in humans.

The binding of four alkaloids with human serum albumin (HSA) was investigated by isothermal titration calorimetry (ITC), spectroscopy and molecular docking techniques. The findings demonstrated that theophylline or caffeine can bind to HAS, respectively. The number of binding sites and binding constants are obtained. The binding mode is a static quenching process. The effects of steric hindrance, temperature, salt concentration and buffer solution on the binding indicated that theophylline and HSA have higher binding affinity than caffeine. The fluorescence and ITC results showed that the interaction between HSA and theophylline or caffeine is an entropy-driven spontaneous exothermic process. The hydrophobic force was the primary driving factor. The experimental results were consistent with the molecular docking data. Based on the molecular structures of the four alkaloids, steric hindrance might be a major factor in the binding between HSA and these four alkaloids. This study elucidates the mechanism of interactions between four alkaloids and HSA.