Article
Chemistry, Medicinal
Karnesh Jain, Othman Ghribi, Jerome Delhommelle
Summary: The misfolding and aggregation of alpha-synuclein play a crucial role in neurodegenerative disorders, with the formation of fibrils involving various intermediates. Simulation results show that conformational rearrangements of alpha-synuclein at physiological temperature mainly exhibit alpha-helix structures. These findings provide valuable insights for understanding the formation of oligomers in neurodegenerative diseases.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemistry & Molecular Biology
Iga Biskupek, Cezary Czaplewski, Justyna Sawicka, Emilia Ilowska, Maria Dzierzynska, Sylwia Rodziewicz-Motowidlo, Adam Liwo
Summary: The UNited RESidue (UNRES) model was used to study the aggregation behavior of 20 peptides with different lengths. The majority of peptides showed inter-strand beta-sheet formation, except for glutamine- and asparagine-rich peptides, which require modification of the UNRES model.
Article
Multidisciplinary Sciences
Emma C. Carroll, Naomi R. Latorraca, Johanna M. Lindner, Brendan C. Maguire, Jeffrey G. Pelton, Susan Marqusee
Summary: The study reveals the effects of ubiquitination on the stability of substrate proteins, indicating that the mechanisms of action of ubiquitination at different sites vary and strongly depend on the local context. Different ubiquitination sites can lead to distinct structural changes and thermodynamic effects, which can be used to guide the design of proteins and therapeutic drugs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Krzysztof Kuczera, Robert Szoszkiewicz, Christopher Shaffer, Gouri Jas
Summary: In this study, we used molecular dynamics and replica-exchange simulations to investigate the folding of the GB1 hairpin peptide in aqueous solution. The results supported a cooperative zipper folding model and provided insights into the formation of hydrogen bonds and hydrophobic contacts during the folding process. Additionally, kinetic models constructed using the Optimal Dimensionality Reduction approach revealed the folding and unfolding times, as well as the formation of transition states and off-path intermediates.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Gokul Govind, E. C. Nayana, Padmesh Anjukandi
Summary: The folding of a 16 residue polypeptide, a beta-hairpin in B1 domain of protein G, is influenced by various factors including backbone H-bond network, side chain H-bonds, and alignment of hydrophobic group side chains. Hydrophobic group side chain interactions are crucial in holding the beta-hairpin together, while denaturant urea affects the backbone H-bonds of GB1-hairpin. In the presence of strong hydrophobic interactions and consistent side chain H-bonding network, the denaturation process is slower compared to proteins without these interactions.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Multidisciplinary Sciences
Son Tung Ngo, Khanh B. Vu, Minh Quan Pham, Nguyen Minh Tam, Phuong-Thao Tran
Summary: The winged-helix domain of wMUS81 is a potential cancer drug target that can be inhibited by marine fungi compounds through forming strong binding affinity. Eight compounds were identified as capable of preventing wMUS81 conformation by interacting with the enzyme via perturbation approach. The electrostatic interaction is the main factor in the binding process of ligands to wMUS81, with specific residues forming non-bonded contacts and hydrogen bonds with inhibitors.
ROYAL SOCIETY OPEN SCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Ali A. Alizadehmojarad, Sergei M. Bachilo, R. Bruce Weisman
Summary: Aqueous suspensions of single-wall carbon nanotubes coated by ssDNA were analyzed to determine the absolute average concentrations of both components and the absorptivity values of the nanotubes. The results provide a method to measure the absolute concentrations of similar SWCNT samples in aqueous SDS using simple spectrophotometry. The study also quantifies the mass ratio of ssDNA to SWCNT and compares experimental results with molecular dynamics simulations.
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
Multidisciplinary Sciences
Rajeswari Appadurai, Jayashree Nagesh, Anand Srivastava
Summary: The study introduces a parallel-tempering method that utilizes accelerated water dynamics for efficient and accurate conformational sampling across a wide variety of proteins, demonstrating successful application to large metamorphic proteins and highly disordered proteins with good fit to experimental data.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Jinzen Ikebe, Munenori Suzuki, Aya Komori, Kaito Kobayashi, Tomoshi Kameda
Summary: This paper presents a method called MSPER for enhancing the regioselectivity of substrate reaction sites by destabilizing binding poses for byproducts while maintaining those for target products. Applying MSPER to cytochrome P450 CYP102A1 (BM3) and two substrates resulted in successfully enhancing the regioselectivity for four target products with different reaction sites.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Hongli Liu, Qin Li, Chunmei Xiong, Haiyang Zhong, Qianqian Zhang, Huanxiang Liu, Xiaojun Yao
Summary: The study explores how pS202/pT205/pS208 triple phosphorylations affect the structure of tau protein, showing that it decreases conformational diversity and disrupts key hydrogen bonds and network structures, ultimately leading to tau aggregation at an atomic level.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Chemistry, Physical
Valerio Rizzi, Simone Aureli, Narjes Ansari, Francesco Luigi Gervasio
Summary: Enhanced sampling techniques, such as using collective variables (CVs) or parallel tempering, have greatly advanced molecular dynamics simulations for studying rare events and calculating free energy differences. We propose a replica exchange method called OneOPES that combines the advantages of multireplica simulations and CV-based enhanced sampling, providing an efficient and robust framework for complex systems.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Biochemistry & Molecular Biology
Ameya Harmalkar, Jeffrey J. Gray
Summary: Computational docking methods can provide structural models of protein-protein complexes, but protein backbone flexibility can hinder accurate predictions. Recent advances include enhanced sampling techniques and internal coordinate formulations to address the issue of protein backbone flexibility.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(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
Biochemistry & Molecular Biology
Yu Zou, Lulu Guan
Summary: This study utilized molecular dynamics simulations to demonstrate that acetylation of K280 enhances the aggregation capability of PHF6* peptides, increasing their beta-sheet structure propensity and inter-molecular interactions. This leads to more ordered beta-sheet-rich conformations of the PHF6* assemblies and decreases structural diversity, ultimately promoting the aggregation of PHF6*.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Chemistry, Physical
James A. Ross-Naylor, Milan Mijajlovic, Hu Zhang, Mark J. Biggs
JOURNAL OF PHYSICAL CHEMISTRY B
(2017)
Article
Chemistry, Physical
James A. Ross-Naylor, Milan Mijajlovic, Mark J. Biggs
JOURNAL OF PHYSICAL CHEMISTRY B
(2020)