Article
Chemistry, Multidisciplinary
Anji Babu Kapakayala, Nisanth N. Nair
Summary: In this study, a new hybrid method combining WSMTD and REST2 is proposed to speed up conformational sampling and free energy calculation. The method employs a divide-and-conquer strategy to independently sample high-dimensional slices of a free energy surface and enhance sampling of slow degrees of freedom through replica exchange. The combined simulations are used to compute probability distributions of CVs and obtain the free energy surface with improved accuracy and quick convergence.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Xiaorong Liu, Xiping Gong, Jianhan Chen
Summary: Efficient sampling of protein conformational space is crucial for quantitative simulations. The MSES-IT method allows independent control of atomic and CG simulation temperatures, improving both sampling efficiency and structural transition rates. This new approach facilitates faster reversible transitions at the atomic level, leading to significant improvements in generating converged conformational ensembles compared to the original MSES scheme.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Lorenzo Casbarra, Piero Procacci
Summary: The study demonstrates that Autodock4 performs surprisingly well in absolute binding free energy predictions, outperforming expensive molecular dynamics or quantum chemistry techniques, with an extremely favorable cost-benefit ratio. Interesting features of Autodock4 predictions are revealed, providing valuable insights on the overall reliability of docking screening campaigns in drug discovery projects.
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2021)
Article
Biochemistry & Molecular Biology
Ai Shinobu, Suyong Re, Yuji Sugita
Summary: Molecular dynamics (MD) simulations are used to study biological processes, but conventional methods are not effective for slow dynamics. Researchers applied a two-dimensional replica-exchange MD method and optimized the simulation protocols to achieve accurate results and good random sampling.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Computer Science, Interdisciplinary Applications
A. E. Macias-Medri, Carlos E. Fiore, M. G. E. da Luz
Summary: This work presents a comprehensive analysis of key elements determining the efficiency of Simulated Tempering implementations for lattice models, including the proper choice of replica temperature set, quantity of replicas, and estimation of weight factors. Tests are proposed to validate different ST implementations and characterize convergence and fluctuations of thermodynamic estimators. A new procedure to calculate critical temperatures is developed by combining the ST method with fixed exchange frequency protocol.
COMPUTER PHYSICS COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Wioletta Brankiewicz, Umesh Kalathiya, Monikaben Padariya, Katarzyna Wegrzyn, Maciej Prusinowski, Joanna Zebrowska, Agnieszka Zylicz-Stachula, Piotr Skowron, Marek Drab, Mariusz Szajewski, Maciej Ciesielski, Malgorzata Gawronska, Anoop Kallingal, Mariusz Makowski, Maciej Baginski
Summary: This work discusses the potential anticancer targets of shelterin proteins, particularly the blocking of TRF1 protein by peptidomimetic molecules. The interaction between TRF1 and TIN2 proteins is crucial for telomere function, and our modified peptide molecules can disrupt this interaction. The disruption of the shelterin complex by our molecule led to cellular senescence in breast cancer cells, making our compounds useful for targeting TRF proteins.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Piotr Chyzy, Marta Kulik, Suyong Re, Yuji Sugita, Joanna Trylska
Summary: Short, structured fragments of non-coding mRNA may act as molecular switches upon binding specific ligands, regulating the translation of proteins encoded downstream this mRNA sequence. The study reveals that nucleobase mutations in the riboswitch can significantly affect the affinity and efficiency of ligand regulation, with specific mutations altering the binding site position of neomycin and increasing its flexibility.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Spectroscopy
Nikki Kuhar, Sanchita Sil, Siva Umapathy
Summary: Proteins, responsible for various biological processes, must maintain correct folding to avoid diseases. Raman spectroscopy techniques, including ROA, provide insights into protein structure and conformational changes, helping differentiate between proteins and understand subtle changes in their conformation. Techniques and data analyses advancements in Raman spectroscopic studies of proteins continue to be explored for a deeper understanding of protein structures.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2021)
Article
Medicine, Research & Experimental
Faisal Mahmood, Ruixian Xu, Maher Un Nisa Awan, Yuzhu Song, Qinqin Han, Xueshan Xia, Jinyang Zhang
Summary: The role of PDIA3 in catalyzing disulphide bonds, acting as a chaperone, and its association with cancer, cellular stress, and viral infections is highlighted. Inhibitors targeting PDIA3 show potential in interfering with viral infections, suggesting a promising avenue for future research in combating viral diseases.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Chemistry, Physical
Carla F. Sousa, Robert A. Becker, Claus-Michael Lehr, Olga V. Kalinina, Jochen S. Hub
Summary: Molecular dynamics simulations were used to study solute permeation across biological membranes. The potential of mean force (PMF) for solute permeation was computed using enhanced sampling techniques such as umbrella sampling (US). However, obtaining converged PMFs for bulky drug-like permeants remains challenging and often requires long simulation times. Simulated tempering-enhanced umbrella sampling (STeUS) was employed to improve the convergence of PMF calculations and reduce the computational cost of routine high-throughput studies of drug permeability.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Review
Microbiology
Elena Smertina, Robyn N. N. Hall, Nadya Urakova, Tanja Strive, Michael Frese
Summary: Caliciviridae is a family of viruses with 11 different genera that can infect a wide range of animal hosts. The non-structural proteins of these viruses may have evolved independently to counteract host immune responses. Studying these proteins is challenging due to the inability of many caliciviruses to grow in cell culture, but recombinant proteins have provided insight into their properties.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Oncology
Simona Taverna, Anna Masucci, Giuseppe Cammarata
Summary: This review focuses on the potential applications of piRNAs as biomarkers in different cancer types. piRNAs not only play key roles in germ line cells but also regulate protein-coding genes and are associated with various diseases, including cancer. Recent studies have found that piRNAs are also present in extracellular vesicles, providing a new avenue for early diagnosis and personalized medicine.
Article
Chemistry, Physical
Vojtech Mlynsky, Michal Janecek, Petra Kuhrova, Thorben Frohlking, Michal Otyepka, Giovanni Bussi, Pavel Banas, Jiri Sponer
Summary: Atomistic molecular dynamics simulations are widely used in studying RNA structural dynamics, but they still face challenges in terms of accuracy of empirical potentials and sampling limitations. In this study, the combination of REST2 and well-tempered metadynamics (ST-MetaD) is shown to improve sampling efficiency by at least two orders of magnitude. Moreover, modifications to the nonbonded terms of the AMBER OL3 RNAff potential are found to stabilize the native state of RNA structures.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Thermodynamics
N. Ben Mustapha, I Boumnijel, D. Mihoubi
Summary: This study demonstrates that tempering drying is more effective than continuous drying in reducing energy consumption, improving drying time, energy consumption, and product quality.
JOURNAL OF HEAT TRANSFER-TRANSACTIONS OF THE ASME
(2022)
Article
Engineering, Environmental
Wanli Guo, Ge Chen, Junjie Wang, Fuxian Jian
Summary: The plastic potential and yield functions are vital components of elastoplastic constitutive models. This study proposes a unified function to define the yield and plastic potential surfaces for rockfills, and experimental results validate the reasonableness of this function.
BULLETIN OF ENGINEERING GEOLOGY AND THE ENVIRONMENT
(2022)
Meeting Abstract
Biophysics
Ayori Mitsutake, Hiroshi Takano
BIOPHYSICAL JOURNAL
(2018)
Article
Chemistry, Physical
Yutaka Maruyama, Ayori Mitsutake
JOURNAL OF PHYSICAL CHEMISTRY B
(2018)
Article
Chemistry, Physical
Hiroshi Fujisaki, Kei Moritsugu, Ayori Mitsutake, Hiromichi Suetani
JOURNAL OF CHEMICAL PHYSICS
(2018)
Article
Chemistry, Physical
Naoyuki Karasawa, Ayori Mitsutake, Hiroshi Takano
JOURNAL OF CHEMICAL PHYSICS
(2019)
Article
Chemistry, Physical
Ayori Mitsutake, Hiroshi Takano
JOURNAL OF CHEMICAL PHYSICS
(2019)
Article
Chemistry, Physical
Shun Yokoi, Ayori Mitsutake
Summary: The study utilized molecular dynamics simulations to investigate the structural changes in OX2R mutants in the active state, identifying a suitable index for evaluating GPCR states and elucidating the structural advantages of TM7 inward movement for GPCR activation.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Physics, Multidisciplinary
Eiji Yamamoto, Takuma Akimoto, Ayori Mitsutake, Ralf Metzler
Summary: The study demonstrates that protein conformational fluctuations directly affect the diffusion properties, showing synchronous fluctuations with diffusivity. The radius of gyration of proteins exhibits 1/f fluctuations. The validity of the Stokes-Einstein-type relation appears to be a general property based on analysis of different protein types.
PHYSICAL REVIEW LETTERS
(2021)
Review
Biophysics
Shun Yokoi, Ayori Mitsutake
Summary: In this review, we investigated the dynamics of the orexin 2 receptor using microsecond-scale molecular dynamics simulations. We observed characteristic conformational changes in a mutant and examined the evaluation index for the active and inactive states of class A G protein-coupled receptors. We also discussed the activation mechanism by comparing the results with the structure obtained from cryo-electron microscopy.
BIOPHYSICAL REVIEWS
(2022)
Article
Chemistry, Medicinal
Norio Yoshida, Yutaka Maruyama, Ayori Mitsutake, Akiyoshi Kuroda, Ryo Fujiki, Kodai Kanemaru, Daisuke Okamoto, Alexander E. Kobryn, Sergey Gusarov, Haruyuki Nakano
Summary: The binding process of ACE2 to the RBD of the SARS-CoV-2 spike protein was investigated using molecular dynamics simulation and theory. The process consists of protein-protein approaching and structural rearrangement steps. The interprotein interaction energy decreased as the proteins approached, while the solvation free energy increased. The glycan of ACE2 first established a hydrogen bond with the RBD, followed by a rapid increase in interprotein hydrogen bonds. The presence of hydrogen bonds bridged by water molecules on the RBD-ACE2 interface was revealed by the solvent's spatial distribution function. Principal component analysis showed a pronounced conformational change in ACE2, while there was no significant change in RBD.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biology
Hiroshi Fujisaki, Hiromichi Suetani, Luca Maragliano, Ayori Mitsutake
Summary: In this study, we applied the non-Markov-type analysis to investigate the state-to-state transitions of the small artificial protein chignolin. The obtained time scales were consistent with previous results obtained using weighted ensemble simulations. Furthermore, we utilized diffusion map analysis to cluster the conformational states of chignolin and found that it provided similar results to relaxation mode analysis for the eigenvectors. We also demonstrated the usefulness of applying diffusion map analysis to shorter trajectories for characterizing the conformational changes of chignolin.
Article
Chemistry, Medicinal
Yutaka Maruyama, Ryo Igarashi, Yoshitaka Ushiku, Ayori Mitsutake
Summary: We used moving root-mean-square deviation (mRMSD) as a method for analyzing protein dynamics without a reference structure. This method calculates the RMSD of structure between two time points and analyzes protein dynamics behavior through time series analysis. Applying this method to Trp-cage trajectory, we found regions of stable states and a characteristic structure with hydrogen bonds. We also determined that >= 20 ns is an appropriate time interval for investigating protein dynamics using mRMSD. Applying this method to NuG2 protein, we detected regions of metastable states in addition to the stable state, making it applicable to proteins with unknown stable structures.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Ayori Mitsutake
Meeting Abstract
Biochemistry & Molecular Biology
Shun Yokoi, Ayori Mitsutake
Article
Chemistry, Multidisciplinary
Yutaka Maruyama, Shunpei Koroku, Misaki Imai, Koh Takeuchi, Ayori Mitsutake
Review
Biophysics
Yutaka Maruyama, Hiroshi Takano, Ayori Mitsutake
BIOPHYSICS AND PHYSICOBIOLOGY
(2019)
