Article
Biochemistry & Molecular Biology
Charles Eldrid, Mire Zloh, Constantina Fotinou, Tamas Yelland, Lefan Yu, Filipa Mota, David L. Selwood, Snezana Djordjevic
Summary: Vascular endothelial growth factors (VEGFs) are essential regulators for blood and lymphatic vessels, interacting with neuropilins and tyrosine kinase receptors. The selectivity of neuropilins and VEGF receptors in binding to VEGF proteins affects their physiological roles. Studies have shown that conformational preferences of VEGF-derived peptides beyond the C-terminal arginine contribute to the ligand selectivity of neuropilins. These findings have implications for designing selective antagonists of neuropilin functions.
Article
Biochemistry & Molecular Biology
Youness El Bakri, Shaaban K. Mohamed, Sajjad Ahmad, Mustafa R. Albayati, Sahar M. Elgarhy, Chin-Hung Lai, Joel T. Mague
Summary: This study reports the synthesis of two new hydrazide derivatives and investigates their properties and anti-inflammatory potential through computational studies. The results show that these compounds have stable structures and high binding affinity.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2022)
Article
Chemistry, Physical
Zhiyi Wu, Philip C. Biggin
Summary: Absolute binding free-energy calculations play a crucial role in drug design, but accuracy is of utmost importance. This study explores the most suitable approach for simulation boxes containing lipid bilayers, and introduces the Rocklin correction method for lipid bilayer systems.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Biochemistry & Molecular Biology
Sophie I. Williams, Xiulian Yu, Tao Ni, Robert J. C. Gilbert, Phillip J. Stansfeld
Summary: Perforin-like proteins (PLPs) play important roles in mechanisms related to parasitic diseases caused by apicomplexan parasites. This study focuses on the comparison of Plasmodium vivax PLP1 and PLP2 with T. gondii PLP1, revealing significant differences in their binding interactions with lipid bilayers. The study highlights the substantial diversity in the biophysical properties of APCI3 domains of apicomplexan PLPs, which have implications for their cell targeting and membrane-binding activities in parasitic life cycles and diseases.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Julius Bogomolovas, Jennifer R. Fleming, Barbara Franke, Bruno Manso, Bernd Simon, Alexander Gasch, Marija Markovic, Thomas Brunner, Ralph Knoll, Ju Chen, Siegfried Labeit, Martin Scheffner, Christine Peter, Olga Mayans
Summary: The study focused on the structure and function of the titin node, finding that MuRF1-mediated ubiquitination significantly affects the trophic response of the myofibril, which may be influenced by the mechanical state of the sarcomere.
Article
Chemistry, Physical
Abinash Kumar, Jonathon N. Baker, Preston C. Bowes, Matthew J. Cabral, Shujun Zhang, Elizabeth C. Dickey, Douglas L. Irving, James M. LeBeau
Summary: Scanning transmission electron microscopy is used to quantify the structural complexity of relaxor ferroelectric systems, revealing the spatial correlation between nanoscale heterogeneities and local polarization. Three main contributions related to Ti content include chemical order, oxygen octahedral tilt, and oxygen octahedral distortion, which disrupt long-range polarization and lead to nanoscale domain formation and the relaxor response. Nanoscale regions of monoclinic-like distortion directly correlate with Ti content and electromechanical performance, validating models needed for the development of the next generation of relaxor ferroelectrics.
Article
Chemistry, Multidisciplinary
Sarah N. Spisak, Zheng Zhou, Shuyang Liu, Qi Xu, Zheng Wei, Kenta Kato, Yasutomo Segawa, Kenichiro Itami, Andrey Yu. Rogachev, Marina A. Petrukhina
Summary: The stepwise chemical reduction of a molecular warped nanographene allowed the isolation of three different reduced states, providing a unique series of nanosized carbanions for in-depth structural analysis. The 3D molecular electrostatic potential maps identified the negative charge localization at the central part of the nanographene surface, where selective coordination of Cs+ ions is confirmed crystallographically. The in-depth theoretical investigation revealed a complex response of the nanographene to the stepwise electron acquisition, resulting in notable changes in the electronic structure and site-dependent aromaticity of the resulting carbanions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Marharyta Blazhynska, Emma Goulard Coderc de Lacam, Haochuan Chen, Benoit Roux, Christophe Chipot
Summary: The study compared the rigorous geometrical route and the shortcut of omitting geometrical restraints in calculating standard binding free energies of protein-protein and protein-ligand complexes using atomistic molecular dynamics simulations. Results showed that simulations strictly following the geometrical route matched experimental measurements, while simulations without geometrical restraints converged poorly and yielded inconsistent results. This suggests the importance of including geometrical restraints for accurate calculations in molecular dynamics simulations.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Shotaro Kamata, Akihiro Honda, Ryo Ishikawa, Makoto Akahane, Ayane Fujita, Chihiro Kaneko, Saeka Miyawaki, Yuki Habu, Yui Shiiyama, Kie Uchii, Yui Machida, Takuji Oyama, Isao Ishii
Summary: Currently, there are no available therapeutic drugs for NASH that progresses from nonalcoholic fatty liver via oxidative stress-involved pathways. Three PPAR subtypes (PPARa/d/?) are considered attractive targets, but the development of many investigational drugs has been discontinued due to side effects or lack of efficacy. This study aimed to gain insights into the potency, efficacy, and selectivity against PPARa/d/? of three current and past anti-NASH investigational drugs: lanifibranor, seladelpar, and elafibranor.
Article
Biochemistry & Molecular Biology
Christo N. Nanev, Emmanuel Saridakis, Naomi E. Chayen
Summary: X-ray crystallography is currently the dominant method for determining the structure of proteins and biomolecules. However, it faces challenges in obtaining high-resolution data from small protein crystals. Serial crystallography using XFELs is a promising alternative method that can produce excellent structural data from weakly diffracting objects. In this study, the authors calculate the mean crystal size and growth time needed for batch crystallization, which is the main method for preparing microcrystalline slurries. They also consider the impact of impurities on the growth of microcrystals. Experimental results with lysozyme support the theoretical predictions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Mariia Radaeva, Huifang Li, Eric LeBlanc, Kush Dalal, Fuqiang Ban, Fabrice Ciesielski, Bonny Chow, Helene Morin, Shannon Awrey, Kriti Singh, Paul S. Rennie, Nada Lallous, Artem Cherkasov
Summary: The mutation-driven transformation of anti-androgen drugs into receptor agonists poses a challenge for prostate cancer treatment. We developed inhibitors targeting the receptor's DNA-binding domain and identified a few that exhibited partial agonistic effects towards mutated forms of the receptor. By studying the molecular basis, we designed derivatives to eliminate cross-reactivity with the receptor's androgen binding site while maintaining anti-DNA-binding domain potency.
Article
Biochemistry & Molecular Biology
Jinying Cheng, Xue Yin, Lulu Wang, Xianxian Liu, Fang Yang, Liguo Zhang, Tonggang Liu
Summary: This study investigates the molecular mechanism of species-selective targeting of fungal versus human HSP90 triggered by the compound A11. The results provide insights into the conformational changes and binding affinities of compound A11 to fungal and human HSP90 and identify key residues for favorable binding. This study has important implications for the development of selective inhibitors targeting fungal HSP90.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Letter
Chemistry, Multidisciplinary
Ning Liu, Oleg Mikhailovskii, Nikolai R. Skrynnikov, Yi Xue
Summary: A pipeline based on molecular dynamics (MD) has been developed to emulate the process of determining protein crystallographic structures from diffraction photographs. Using a lysozyme structure as a template, a supercell containing 125 crystal unit cells with 1000 protein molecules and solvent was constructed. MD trajectories at 298 K and 250 K were simulated and used to generate diffraction photographs, which were then fed into the standard pipeline for structure determination. The resulting structures were highly consistent with the MD model and the original experimental structure. This methodology has potential applications in refining crystal structures and extracting dynamic information from diffraction data or diffuse scattering.
Article
Chemistry, Multidisciplinary
Zheng Zhou, Jesus M. Fernandez-Garcia, Yikun Zhu, Paul J. Evans, Rafael Rodriguez, Jeanne Crassous, Zheng Wei, Israel Fernandez, Marina A. Petrukhina, Nazario Martin
Summary: Chemical reduction of pi-conjugated bilayer nanographene using K and Rb resulted in the formation of two new ion compounds, demonstrating an uncommon hydrogenation process in graphene that leads to changes and slippage in the bilayers. This provides a new insight into the structure and properties of graphene.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Abigail R. Orun, Ethan T. Shields, Sara Dmytriw, Ananya Vajapayajula, Caroline K. Slaughter, Christopher D. Snow
Summary: Researchers have designed isoreticular cocrystals as scaffolds for DNA-binding molecules. These cocrystals have tunable DNA-DNA junctions and can accommodate different guest molecules during crystallization. The design principles can be applied to existing cocrystals to develop programmable scaffolds for DNA-binding molecules.
Article
Chemistry, Medicinal
Bhautikkumar Patel, Rachel Kerr, Alpeshkumar K. Malde, Matthew Zunk, Timothy D. H. Bugg, Gary Grant, Santosh Rudrawar
Editorial Material
Biochemistry & Molecular Biology
Alan Edward Mark, Christine Peter
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2020)
Article
Chemistry, Medicinal
Vivek Makwana, Philip Ryan, Alpeshkumar K. Malde, Shailendra Anoopkumar-Dukie, Santosh Rudrawar
Summary: OGT is a key enzyme involved in the modification of various nuclear and cytosolic proteins with O-GlcNAc. Rational design of bisubstrate analogue inhibitors for OGT sheds light on the potential role of OGT in regulating cellular functions.
Review
Chemistry, Physical
Wilfred F. van Gunsteren, Xavier Daura, Patrick F. J. Fuchs, Niels Hansen, Bruno A. C. Horta, Philippe H. Huenenberger, Alan E. Mark, Maria Pechlaner, Sereina Riniker, Chris Oostenbrink
Summary: Computer simulations of molecular systems play a crucial role in chemistry, biology, and physics, but it is important to consider uncertainty and errors affecting the calculated properties; advantages and shortcomings of commonly used assumptions and approximations in simulating bio-molecular systems should be taken into account; developers can improve simulation quality by discussing ways to facilitate and expand research involving bio-molecular simulations.
Article
Neurosciences
Matthew D. Figley, Weixi Gu, Jeffrey D. Nanson, Yun Shi, Yo Sasaki, Katie Cunnea, Alpeshkumar K. Malde, Xinying Jia, Zhenyao Luo, Forhad K. Saikot, Tamim Mosaiab, Veronika Masic, Stephanie Holt, Lauren Hartley-Tassell, Helen Y. McGuinness, Mohammad K. Manik, Todd Bosanac, Michael J. Landsberg, Philip S. Kerry, Mehdi Mobli, Robert O. Hughes, Jeffrey Milbrandt, Bostjan Kobe, Aaron DiAntonio, Thomas Ve
Summary: SARM1 is a nicotinamide adenine dinucleotide (NAD+)-cleaving enzyme that is activated by an increase in the ratio of NMN to NAD+, triggering axon destruction. The structural analysis showed that both NMN and NAD+ compete for binding to the auto inhibitory N-terminal armadillo repeat (ARM) domain of SARM1.
Article
Chemistry, Physical
Stephen Sanderson, George Vamvounis, Alan E. Mark, Paul L. Burn, Ronald D. White, Bronson W. Philippa
Summary: This study used kinetic Monte Carlo simulations to investigate exciton diffusion in Ir(ppy)(3):CBP blend films, revealing the effects of guest concentration and exciton density on system properties. The simulations suggest that triplet diffusion mainly occurs through guest-guest Dexter transfer and that concentration quenching of triplets has a negligible effect at high exciton densities due to triplet-triplet annihilation.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Multidisciplinary Sciences
Max T. B. Clabbers, Susannah Holmes, Timothy W. Muusse, Parimala R. Vajjhala, Sara J. Thygesen, Alpeshkumar K. Malde, Dominic J. B. Hunter, Tristan Croll, Leonie Flueckiger, Jeffrey D. Nanson, Md Habibur Rahaman, Andrew Aquila, Mark S. Hunter, Mengning Liang, Chun Hong Yoon, Jingjing Zhao, Nadia A. Zatsepin, Brian Abbey, Emma Sierecki, Yann Gambin, Katryn J. Stacey, Connie Darmanin, Bostjan Kobe, Hongyi Xu, Thomas Ve
Summary: MyD88 and MAL are TLR adaptors that induce pro-inflammatory cytokine production, with the TIR domain of MAL forming filaments in vitro that nucleate the assembly of crystalline arrays of the MyD88 TIR domain. The structures of these assemblies were determined using MicroED and SFX techniques, showing the importance of the MyD88 interface residues for TLR4 signaling in vivo. The study provides insight into TLR signal transduction and compares the MicroED and SFX techniques.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Shaobo Zhang, Cheng Li, Robert G. Gilbert, Alpeshkumar K. Malde
Summary: This study used molecular dynamics simulations to build a model of the binding between rice GBSS and amylose, finding that starch/amylose fragments with 5 or 6 glucose units were suitable for modeling starch binding. Removing an interdomain disulfide on GBSS was found to affect the binding stability, and key residues that could affect the binding ability were identified.
Article
Engineering, Environmental
Tu Lan, Peng Wu, Ziyi Liu, Martin Stroet, Jiali Liao, Zhifang Chai, Alan E. Mark, Ning Liu, Dongqi Wang
Summary: This study investigates the dynamics of humic acid (HA) in a water solution and its dependence on pH, temperature, and concentration using molecular dynamics (MD) simulations. The results reveal the compact conformation of HA in water and pH-dependent aggregation. Experimental data support the simulation results.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Larnii S. Booth, Eloise Browne, Nicolas P. Mauranyapin, Lars S. Madsen, Shelley Barfoot, Alan Mark, Warwick P. Bowen
Summary: The structural dynamics of macromolecules play a vital role in microbiological processes. Optical sensors have recently been used to measure the dynamic polarizability of single-molecules. This study presents a method to predict the dynamic polarizability from the atomic configuration of macromolecules, allowing the connection between measured polarizability and molecular structure.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Physical
Stephen Sanderson, George Vamvounis, Alan E. Mark, Paul L. Burn, Ronald D. White, Bronson W. Philippa
Summary: Solution-processing of organic light-emitting diode films has potential advantages over vacuum-deposition, but may result in lower device performance. Molecular dynamics simulations were used to study solvent evaporation during solution processing and its effects on charge transport and exciton dynamics.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Chemistry, Applied
Xiaoyan Tan, Shaobo Zhang, Alpeshkumar K. Malde, Xinle Tan, Robert G. Gilbert
Summary: This study investigates the effects of endogenous proteins on starch digestion kinetics in chickpeas. It identifies potential proteinaceous alpha-amylase inhibitors belonging to albumin, globulin, and glutelin and explores their binding mechanisms with porcine pancreatic alpha-amylase (PPA) using docking simulation. The results show that small peptides (<3 kDa) from the hydrolysis of endogenous proteins exhibit strong inhibitory activity on PPA. It is found that the different types of alpha-AIs inhibit PPA activity by interacting with specific regions of the enzyme, hindering the formation of enzyme-starch complexes and reducing starch digestibility.
FOOD HYDROCOLLOIDS
(2022)
Article
Chemistry, Inorganic & Nuclear
Anil K. Gorle, Alpeshkumar K. Malde, Chih-Wei Chang, Premraj Rajaratnam, Mark von Itzstein, Susan J. Berners-Price, Nicholas P. Farrell
Summary: [H-1, N-15] HSQC 2D NMR spectroscopy was used to study the aquation and subsequent coordinate covalent binding of the trinuclear clinical agent triplatin with two disaccharides, GlcNS(6S)-GlcA and GlcNS(6S)-IdoA(2S). The rate constant for sulfate displacement of the aqua ligand is higher than that for carboxylate displacement. Molecular dynamics calculations suggest that extra hydrogen-bonding interactions with the more sulfated disaccharide may prevent or diminish sulfate binding of the triplatin moiety.
INORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Shaobo Zhang, Xiaolei Fan, Alpeshkumar K. Malde, Robert G. Gilbert
Summary: This study used molecular dynamics simulations and free energy calculations to predict the binding of different GBSSI mutants to amylose fragments and to predict the effects of mutations on enzyme activity. It was found that mutants with negative binding energy are more likely to have higher enzyme activity and amylose content. This research is helpful in the development of grains with improved functional properties.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Multidisciplinary
Benjamin Bailly, Anil K. Gorle, Larissa Dirr, Alpeshkumar K. Malde, Nicholas P. Farrell, Susan J. Berners-Price, Mark von Itzstein
Summary: TriplatinNC is an antiviral agent that protects cells from viral entry by forming adducts with cell-surface glycosaminoglycans, opening new directions for metalloshielding antiviral drug development.
CHEMICAL COMMUNICATIONS
(2021)
