Article
Chemistry, Medicinal
P. Bernat Szabo, Francesc Sabanes Zariquiey, Juan J. Nogueira
Summary: By conducting ensemble docking of over 2000 FDA-approved drugs on the SARS-CoV-2 RdRp protein and introducing dynamic effects and cosolvent simulations, this study improved docking results by discovering unique binding pockets, providing a more suitable ligand selection method, and is expected to enhance virtual screening efficiency in future drug discovery projects.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemistry & Molecular Biology
Dorota Kowalska, Joanna Dolzonek, Krzysztof Zamojc, Sergey A. Samsonov, Martyna Maszota-Zieleniak, Joanna Makowska, Piotr Stepnowski, Anna Bialk-Bielinska, Dariusz Wyrzykowski
Summary: Human serum albumin (HSA) plays a crucial role in binding low-molecular-weight compounds and facilitating their distribution in living organisms. This study investigates the impact of counter-ions, such as [B (CN)4]- and [C(CN)3]-, on the affinity of [IM1-12]+ towards HSA. Experimental methods and computational approaches are used to analyze protein-ligand interactions and the thermal stability of resulting complexes. The findings provide valuable insights into the presence of globular proteins and ionogenic compounds in the environment and living organisms.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Physical
Dominik Sidler, Michael Ruggenthaler, Christian Schaefer, Enrico Ronca, Angel Rubio
Summary: This article provides a brief introduction to the theoretical complexity of polaritonic chemistry and emphasizes the importance of ab initio methods. It proposes novel ideas and research avenues regarding quantum collectivity and resonance phenomena in reaction rates under vibrational strong coupling. A computationally efficient Langevin framework based on quantum electrodynamical density-functional theory is also suggested, revealing cavity-induced non-equilibrium nuclear dynamics. Overall, the latest ab initio results suggest a paradigmatic shift in the understanding of ground-state chemical reactions under vibrational strong coupling.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Chemistry, Physical
Stanly Paul, Swathi Nadendla, M. Elizabeth Sobhia
Summary: The emergence of distinct variants has turned the COVID-19 pandemic into a global health challenge. Omicron, a new variant, has been classified as a variant of concern by the World Health Organization due to its higher mutation rate and accelerated human infection. Inhibition of the interaction between the receptor binding domain (RBD) and the human angiotensin converting enzyme-2 (ACE(2human)) receptor has been proven effective in inhibiting viral infection. Through molecular dynamics simulation, our study explores the atomic details and events of RBD-ACE(2human) interactions, providing insights for the development of therapeutic peptidomimetics targeting omicron.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Multidisciplinary Sciences
R. Tucker Sprenkle, L. G. Silvestri, M. S. Murillo, S. D. Bergeson
Summary: This study validates the assumptions and capabilities of simulations for ion-ion temperature relaxation in strongly coupled Coulomb systems, and invalidates theoretical models in this regime.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Andreas Mardt, Tim Hempel, Cecilia Clementi, Frank Noe
Summary: This study addresses the challenge of modeling the dynamics of large molecular systems by introducing a method that simultaneously decomposes and models the system, providing an effective summary of the complex dynamics. While the issue of learning the dynamical coupling between subsystems still remains, it is a significant step towards learning Ising models of large molecular complexes from simulation data.
NATURE COMMUNICATIONS
(2022)
Review
Chemistry, Physical
Outi Haapanen, Vivek Sharma
Summary: Respiratory complex I plays a crucial role in the electron transport chains of mitochondria and bacteria by efficiently coupling the redox reaction and proton pumping through a unique tunnel, leading to the synthesis of ATP. The separation of redox reaction and proton pumping in space and time raises the question of how these two reactions are so efficiently coupled. Recent structural data and molecular simulations provide insights into how quinone reduction and dynamics may be linked to proton pumping in complex I.
CURRENT OPINION IN ELECTROCHEMISTRY
(2021)
Article
Chemistry, Physical
Junke Wang, Chan Gao, Zilong Xu, Cheng Zhong, Rucheng Dai, Zhongping Wang, Hongzhen Li, Zengming Zhang
Summary: The study investigated the pressure effects on the thermal decay of LLM-105, finding that a weak loading pressure can significantly raise the decomposition temperature. Experimental results were consistent with theoretical predictions.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Chemistry, Medicinal
Osvaldo Burastero, Lucas A. Defelipe, Gabriel Gola, Nancy L. Tateosian, Elias D. Lopez, Camila Belen Martinena, Juan Pablo Arcon, Martin Dodes Traian, Diana E. Wetzler, Isabel Bento, Xavier Barril, Javier Ramirez, Marcelo A. Marti, Maria M. Garcia-Alai, Adrian G. Turjanski
Summary: In this research, computer-aided drug discovery methods were used to explore the interaction between protein kinase G and ligands related to Mycobacterium tuberculosis. Ethanol was used as a solvent in molecular dynamics simulations. Several experiments were conducted to validate the simulation results and identify compounds with inhibitory activity against tuberculosis.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Osvaldo Burastero, Lucas A. Defelipe, Gabriel Gola, Nancy L. Tateosian, Elias D. Lopez, Camila Belen Martinena, Juan Pablo Arcon, Martin Dodes Traian, Diana E. Wetzler, Isabel Bento, Xavier Barril, Javier Ramirez, Marcelo A. Marti, Maria M. Garcia-Alai, Adrian G. Turjanski
Summary: Computer-aided drug discovery methods have a significant impact on the development of therapeutically important small molecules. This study focuses on the use of molecular dynamics simulations in mixed solvents to improve protein-ligand recognition and molecular docking predictions. By using ethanol as a cosolvent, interactions between ligands and protein kinase G were explored, leading to the discovery of potential inhibitors. Various experimental assays confirmed the findings, and the compounds showed significant inhibition of Mycobacterium tuberculosis viability in infected cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Patryk Kuleta, Jonathan Lasham, Marcin Sarewicz, Iwona Ekiert, Vivek Sharma, Robert Ekiert, Artur Osyczka
Summary: This study identifies a dual role of hydrogen bonding in regulating the redox potential of heme in cytochrome bc1, which is essential for maintaining proper function of energy-conserving systems. By stabilizing this hydrogen bond, both the redox potential of the heme and its spin state can be influenced, potentially leading to changes in electron transfer rates and interactions with redox partners. These findings suggest a delicate balance between H-bond stability and heme-protein interactions in fine-tuning the redox properties of heme proteins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Catharine Shipps, H. Ray Kelly, Peter J. Dahl, Sophia M. Yi, Dennis Vu, David Boyer, Calina Glynn, Michael R. Sawaya, David Eisenberg, Victor S. Batista, Nikhil S. Malvankar
Summary: The study demonstrates that amyloid proteins can efficiently transport charges at physiologically relevant potentials without the need for metal cofactors or large driving forces. The conductivity is attributed to a multistep hopping mechanism, with hole transport rate influenced by proton acceptors and proximity to tyrosines. Surprisingly, conductivity increases significantly upon cooling due to higher availability of proton acceptors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pharmacology & Pharmacy
Suk Kyu Ko, Gabriella Bjoerkengren, Carolin Berner, Gerhard Winter, Pernille Harris, Guenther H. J. Peters
Summary: We conducted molecular dynamics simulations to investigate the mechanisms of stabilization and the role of excipients during freeze drying of Reteplase. The simulations revealed that the presence of arginine decreased the aggregation propensity of Reteplase by preventing intermolecular interactions. Additionally, experimental techniques such as nanoDSF, size-exclusion chromatography, and CD spectroscopy were used to study the effect of freeze drying on the protein structure and stability.
Article
Biochemistry & Molecular Biology
Till El Harrar, Benedikt Frieg, Mehdi D. Davari, Karl-Erich Jaeger, Ulrich Schwaneberg, Holger Gohlke
Summary: This study investigates the impact of aqueous ionic liquids on a model enzyme through molecular dynamics simulations and finds that they can affect enzyme activity by modifying local structural stability, eventually leading to perturbations in the catalytic site and protein core. The identification of perturbation pathways and specific interactions with IL ions helps predict variant libraries with improved tolerance to aqueous ionic liquids.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Multidisciplinary Sciences
Prakash Kishore Hazam, Chimanjita Phukan, R. Akhil, Anjali Singh, Vibin Ramakrishnan
Summary: Designing stereochemically diversified antimicrobial peptides showed impressive activity against multidrug-resistant bacterial pathogens. The inclusion of D amino-acids expanded the design space, offering potential for future biomaterial designs, especially antimicrobials, with comparable antimicrobial activity to existing peptide-based antimicrobials.
SCIENTIFIC REPORTS
(2021)
