Article
Chemistry, Medicinal
Rafael G. Viegas, Murilo N. Sanches, Alan A. A. Chen, Fernando V. Paulovich, Angel E. Garcia, Vitor B. P. Leite
Summary: Molecular dynamics (MD) simulations are powerful tools for studying the folding pathways of biomolecules. In this study, we used MD simulations to investigate the folding of an RNA tetraloop and analyzed the dynamics using the energy landscape visualization method (ELViM). Our results provide insights into the folding process of the tetraloop and demonstrate the potential of ELViM for studying biomolecules.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Samik Bose, Samuel D. Lotz, Indrajit Deb, Megan Shuck, Kin Sing Stephen Lee, Alex Dickson
Summary: It has been found that the kinetics of drug binding is more important than thermodynamic quantities in predicting drug efficacy. Therefore, predictive computational models are being developed to optimize compounds based on their kinetics. These models are based on the structural details of the short-lived ligand binding transition states. Experimental observation of transition states is not possible, but recent successes have shown that modeling the ligand binding transition state is feasible. This study focuses on analyzing the unbinding ensembles and the features of ligand binding transition state ensembles (TSEs). The findings highlight the challenges of rational, kinetics-based drug design.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Sho Nagai, Shingo Urata, Kent Suga, Takeshi Fukuma, Yasuo Hayashi, Keisuke Miyazawa
Summary: Water molecules can influence the reactivity and molecular adsorption behavior of oxide surfaces. This study used 3D-AFM and molecular dynamics simulations to observe the hydroxyl (OH) groups and their hydration structures on sapphire and alpha-quartz surfaces at the atomic scale. The results showed that the density and hydrogen-bonding strength of surface OH groups affect their hydration structures. Additionally, the force curves obtained by 3D-AFM revealed that hydration forces intensify at sites where water molecules strongly interact with surface OH groups. This research provides important insights for understanding the interaction between Al2O3 and SiO2 with water molecules and highlights the potential of 3D-AFM in studying atomic-scale hydration structures on different surfaces.
Article
Biochemistry & Molecular Biology
Zineb Elftmaoui, Emmanuelle Bignon
Summary: S-glutathionylation is involved in cell signaling regulation and plays a critical role in cellular processes. However, its effects on protein structure and activity are not well understood. This study provides reliable AMBER parameters for S-glutathionylation and demonstrates their capability in describing the structural properties of S-glutathionylated proteins. These findings offer an important tool for investigating the impact of S-glutathionylation on protein dynamics and function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Oskar Cheong, Michael H. Eikerling, Piotr M. Kowalski
Summary: Classical molecular dynamics simulations were performed to compare water structures with ab initio molecular dynamics simulations. Good agreement was found between the two approaches at the same length and time scales. However, longer trajectories simulated with classical molecular dynamics led to the formation of different, more stable water structures, which were validated with ab initio calculations. This suggests the usefulness and advantage of classical molecular dynamics simulations for sampling more realistic time and length scales in simulations of metal-aqueous solution interfaces.
APPLIED SURFACE SCIENCE
(2022)
Article
Geosciences, Multidisciplinary
Leonore Jungandreas, Cathy Hohenegger, Martin Claussen
Summary: Coarse global climate models fail to reproduce the monsoonal precipitation pattern over North Africa during the mid-Holocene. The first regional, storm-resolving simulations with an idealized mid-Holocene vegetation cover show a northward shift of the West African monsoon and reduced precipitation gradient between the Guinea coast and the Sahara. Soil moisture and precipitation interactions, as well as land surface interactions with the monsoon circulation, are found to be responsible for the changes in monsoonal precipitation.
CLIMATE OF THE PAST
(2023)
Article
Chemistry, Physical
Pei-Yin Lee, Abhilash Sahoo, Silvina Matysiak
Summary: Transmembrane helix folding and self-association are important processes in biological signaling and transportation across biomembranes. This study uses molecular simulations to investigate the folding and dimerization of Glycophorin A (GpA) and its mutants in the presence of Dodecyl-phosphocholine (DPC) micelles. The results reveal independent folding and dimerization events for transmembrane helices and identify specific features responsible for the structural stability of GpA. This work provides a comprehensive understanding of the structural stability of GpA in a micellar environment and demonstrates the potential of computationally efficient models for studying conformational alterations of transmembrane proteins with physiological relevance.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Medicine, Research & Experimental
Farkhad Maksudov, Evgenii Kliuchnikov, Daniel Pierson, M. L. Ujwal, Kenneth A. Marx, Arani Chanda, Valeri Barsegov
Summary: This article investigates the structure-function relationships of PMOs, which are therapeutic RNA mimicking molecules. By utilizing various techniques, such as circular dichroism and molecular dynamics simulations, the solution structures of PMOs were determined. The study reveals that PMOs adopt non-canonical, partially helical, and stable folded structures, and exhibit thermodynamic stability and concentration-dependent viscosity properties.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Chemistry, Physical
Ming Ma, Junjie Song, Yi Dong, Weihai Fang, Lianghui Gao
Summary: In this study, a novel coarse-grained force field was developed to reproduce the structural and thermodynamic properties of triglycerides in bulk phase, as well as at air and water interfaces. The force field accurately reproduced the self-assembled network and diverse molecular conformations of triglycerides in water, and correctly predicted experimental macroscopic thermodynamic properties. This work paves the way for studying complex systems involving triglycerides on a larger scale.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Elena Kolodzeiski, Saeed Amirjalayer
Summary: The study introduces an on-the-fly training algorithm for automating force field parametrization, addressing challenges in highly dynamic and interlocked structures. This method provides a fast, automated scheme for force field parametrization and accurately models equilibrium and out-of-equilibrium properties of flexible molecules.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Chemistry, Medicinal
Marina Minarro-Lleonar, Andrea Bertran-Mostazo, Jorge Duro, Xavier Barril, Jordi Juarez-Jimenez
Summary: Targeted protein degradation is a promising therapeutic strategy, and lenalidomide and pomalidomide are effective drugs in this field. These drugs stabilize the complex between CRBN and neo-substrates, leading to their degradation. The study identifies the role of hydrophobic shielding in stabilizing the CRBN-CK1 alpha complex and demonstrates the relationship between hydrogen bond robustness and binding affinities, providing insights for the design of improved protein degraders.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Hyungmin Jun, Xiao Wang, Molly F. Parsons, William P. Bricker, Torsten John, Shanshan Li, Steve Jackson, Wah Chiu, Mark Bathe
Summary: ATHENA is an open-source software that automatically renders single-stranded DNA scaffold routing and staple strand sequences for any target wireframe DNA origami, expanding the possibilities of designing 3D DNA-based assemblies. The software also allows external editing of sequences and provides atomic-level models for molecular dynamics, coarse-grained dynamics with oxDNA, and other computational chemistry simulation approaches.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Physical
Yang Ge, Xueping Wang, Qiang Zhu, Yuqin Yang, Hao Dong, Jing Ma
Summary: This study proposes a machine learning-guided adaptive parametrization method that develops a mixed atomic and coarse-grained model to precisely regulate the peptide self-assembly. The method significantly reduces computational costs while maintaining qualitative agreement with observed morphologies in experiments.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Physical
Ryan W. Penhallurick, Alliyah Harold, Maya D. Durnal, Toshiko Ichiye
Summary: The study discovered that a single-site mutation from aspartic acid to glutamic acid in dihydrofolate reductase can reverse the pressure-dependent activity, leading to profound changes in protein structure and activity. This mutation alters the coupling between specific structural elements, resulting in changes in correlated motions of the protein.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Chemistry, Physical
Jinyin Zha, Fei Xia
Summary: Simulating the conformations and functions of biological macromolecules using all-atom (AA) models is costly, but a possible solution is to develop hybrid AA/UCG models. In this study, we developed hybrid models and used them to investigate the conformational changes of microtubule-bound tubulins. Results showed the mechanism of selective binding of taxol molecules to microtubules. We also explored the interactions between microtubules and dyneins, demonstrating the potential of the hybrid AA/UCG model in studying complex biological systems.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
