Article
Biochemistry & Molecular Biology
Juan Jose Galano-Frutos, Renzo Torreblanca, Helena Garcia-Cebollada, Javier Sancho
Summary: Molten globule (MG) is a compact, non-native conformation of proteins that plays important roles in protein folding and misfolding. This article presents an atomistic model of MG formed by the apoflavodoxin from the human pathogen Helicobacter pylori, and successfully explains its characteristic spectral and thermodynamic features.
Article
Biochemistry & Molecular Biology
Juan Jose Galano-Frutos, Renzo Torreblanca, Helena Garcia-Cebollada, Javier Sancho
Summary: Molten globule (MG) is a compact, non-native conformation of proteins that has been studied for over 40 years due to its implications in protein folding, cell functions, and misfolding diseases. Researchers have successfully developed an integrative atomistic model of an MG by analyzing stability of mutants and conducting biased molecular dynamics simulations, shedding light on the energetics and roles of these elusive conformations.
Article
Multidisciplinary Sciences
Marc Rico-Pasto, Annamaria Zaltron, Sebastian J. Davis, Silvia Frutos, Felix Ritort
Summary: This study experimentally verifies the existence of a molten globule intermediate in the protein folding process and reveals some thermodynamic properties of this intermediate.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Applied
Lei Wang, Jiayu Wen, Luying Wang, Lianzhou Jiang, Yan Zhang, Xiaonan Sui
Summary: In this study, the conformational changes of SPI induced to form the MG state using polar acid and polar alkaline solutions were investigated. The findings showed that extreme pH treatment can transform SPI into the MG state and enhance its foaming and emulsifying properties, providing a theoretical basis for developing products with excellent foaming and emulsifying properties in the food, pharmaceutical, and cosmetic industries.
FOOD HYDROCOLLOIDS
(2023)
Article
Biochemistry & Molecular Biology
Fernando Bergasa-Caceres, Herschel A. Rabitz
Summary: The folding pathway of the C-terminal domain of the murine prion protein mPrP(90-231) is predicted using the sequential collapse model, revealing the formation of the most populated molten globule-like intermediate and an early non-local contact that promotes the formation of a less stable intermediate. The formation of a dominant non-local contact provides an example of a potential shortcut to the native structure of the prion protein, while the less stable intermediate may serve as an initiation point for folding in three pathogenic mutants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Daraksha Yameen, Seerat Siraj, Zahoor Ahmad Parray, Mohammad Masood, Asimul Islam, Mohammad Mahfuzul Haque
Summary: In this study, the effect of crowding on the conformation of cytochrome c was investigated using synthetic crowders. The results showed that the presence of glucose led to the formation of a molten globule, while the presence of dextran 70 resulted in a pre-molten globule state. These findings suggest that crowders can protect proteins under harsh conditions and have important biological implications.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Multidisciplinary Sciences
R. Charlotte Eccleston, David D. Pollock, Richard A. Goldstein
Summary: Epistasis and cooperativity in protein folding are both influenced by networks of energetic interactions within proteins, and their selection can affect each other. Selection for cooperativity may be crucial for predicting protein structure using epistasis measurements.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Munishwar Nath Gupta, Vladimir N. N. Uversky
Summary: Transitions between unfolded and native states of globular proteins result in the accumulation of intermediate states known as molten globules. These intermediates, including pre-molten globules, wet molten globules, and dry molten globules, play important roles in both structured and intrinsically disordered proteins. This overview highlights the characteristics and significance of molten globules, discusses engineered molten globules, and reviews their formation under macromolecular crowding conditions and interactions with nanomaterials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Barry Robson
Summary: There has been recent success in predicting the folded native structures of proteins, but a de novo approach based on general principles of energy and entropy remains unsolved and is considered a major outstanding issue in modern science.
COMPUTERS IN BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Ricardo Ceron, Mariana Peimbert, Arturo Rojo-Dominguez, Hugo Najera
Summary: This study reveals that lysozyme can form amyloid fibers under specific conditions, and the presence of copper ions inhibits their formation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Biochemistry & Molecular Biology
Chiaki Nishimura, Takeshi Kikuchi
Summary: Protein folding is crucial for its proper function, and this review focuses on the formation of helical structures in globin proteins and the occurrence of non-native and misfolded structures. The research presented aims to characterize the intermediates and the complete folding pathway to understand the mechanisms of misfolding and the role of non-native structures in the folding intermediate. The article also discusses the stabilization and slower folding induced by non-native structures.
Article
Chemistry, Physical
Neha Raina, Ekampreet Singh, Ishfaq Ahmad Ahanger, Mohammad Shahid, Md. Imtaiyaz Israil, Md. Imtaiyaz Hassan, Faizan Ahmad, Amit Kumar Singh, Asimul Islam
Summary: Macromolecular crowding, driven by hard-core repulsions and soft interactions, has both stabilizing and destabilizing effects on protein folding and stability, which has recently gained attention. This study investigated the impact of polyethylene glycol (PEG) on the structure and stability of holo alpha-lactalbumin (alpha-LA), and found significant alterations in secondary and tertiary structure. PEG created a molten globule state in alpha-LA, with hydrophobic patches and a larger hydrodynamic volume. Isothermal titration calorimetry revealed significant binding between holo alpha-LA and PEG 20,000 Da at physiological pH. Protein-crowder interactions should be carefully considered in macromolecular crowding studies, as destabilizing interactions dominated stabilizing exclusion volume effects.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Automation & Control Systems
Biao Wang, Wenjing Wang, Guanglei Meng, Zhihua Qiao, Yuming Guo, Na Wang, Wei Wang, Zhizhong Mao
Summary: This paper proposes a method to improve the predictive performance of molten steel temperature by outlier detection. The method utilizes dynamic outlier ensemble and clustering analysis to select the best base detectors, thus promoting the performance of predictive models.
ENGINEERING APPLICATIONS OF ARTIFICIAL INTELLIGENCE
(2022)
Article
Biochemistry & Molecular Biology
Fenggui Fan, Hao Zhang, Qian Wei, Yahui Wei
Summary: This study reveals the evolutionary conservation of PDI-S between land plants and algal organisms, and elucidates the induction mechanism of AtPDI11 under ER stress and the crucial importance of the D domain for its activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Marc Mora, Stephanie Board, Olivier Languin-Cattoen, Laura Masino, Guillaume Stirnemann, Sergi Garcia-Manyes
Summary: Non-native disulfide bonds are dynamic covalent bridges formed in proteins, which can be detected using mechanical force and are associated with protein function and aggregation diseases.
Review
Chemistry, Multidisciplinary
Adam Hospital, Federica Battistini, Robert Soliva, Josep Lluis Gelpi, Modesto Orozco
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Guillem Portella, Modesto Orozco, Michele Vendruscolo
Article
Chemistry, Physical
Sanja Zivanovic, Genis Bayarri, Francesco Colizzi, David Moreno, Josep Lluis Gelpi, Robert Soliva, Adam Hospital, Modesto Orozco
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2020)
Article
Chemistry, Physical
Sanja Zivanovic, Francesco Colizzi, David Moreno, Adam Hospital, Robert Soliva, Modesto Orozco
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2020)
Article
Chemistry, Physical
David Moreno, Sanja Zivanovic, Francesco Colizzi, Adam Hospital, Juan Aranda, Robert Soliva, Modesto Orozco
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2020)
Article
Multidisciplinary Sciences
Francesco Colizzi, Modesto Orozco
Summary: The study utilizes coevolutionary information, multiscale molecular simulations, and free-energy methods to quantify allosteric regulations of protein complexes, revealing a simple ON/OFF regulation of AC by stimulatory and inhibitory G proteins. The approach provides a general strategy for exploring uncharted functional space in complex biomolecular regulations.
Article
Biochemical Research Methods
Genis Bayarri, Pau Andrio, Adam Hospital, Modesto Orozco, Josep Lluis Gelpi
Summary: The BioBB REST API extends and complements the BioBB library, offering programmatic access to the collection of biomolecular simulation tools included in the BioExcel Building Blocks library.
Article
Biochemistry & Molecular Biology
Genis Bayarri, Pau Andrio, Modesto Orozco, Josep Lluis Gelpi
Summary: BioExcel Building Blocks Workflows is a web-based graphical user interface that provides access to a collection of pre-configured biomolecular simulation workflows. It offers a high level of interactivity and integrates multiple tools and features to streamline common processes in biomolecular simulation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Physical
Mirko Paulikat, Juan Aranda, Emiliano Ippoliti, Modesto Orozco, Paolo Carloni
Summary: The authors used classical molecular dynamics and quantum mechanics/molecular mechanics methods to investigate proton transfer processes in N-ESI/IM-MS, and validated the simulation results with experimental data. The study revealed that the distribution of protons depends on the hydration level of the analytes and the size of droplets formed during electrospray experiments.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Jose L. Neira, Athi N. Naganathan, Noel Mesa-Torres, Eduardo Salido, Angel L. Pey
Summary: The mutations G170R and I244T are the most common disease causes in primary hyperoxaluria type I. This study found that phosphorylation of T9 may affect the conformation of NTT-AGT and synergize with PH1-causing mutations to promote aggregation in a genotype-specific manner.
Article
Biochemistry & Molecular Biology
Aakash Basu, Dmitriy G. Bobrovnikov, Basilio Cieza, Juan Pablo Arcon, Zan Qureshi, Modesto Orozco, Taekjip Ha
Summary: In this study, we comprehensively characterized the mechanical code of DNA using high-throughput experimental methods and developed a physical model to describe the sequence and methylation dependence of DNA deformation. Our measurements and model validations demonstrated that sequence and epigenetic modifications can encode regulatory information in diverse contexts.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Israel Serrano-Chacon, Bartomeu Mir, Lorenzo Cupellini, Francesco Colizzi, Modesto Orozco, Nuria Escaja, Carlos Gonzalez
Summary: We studied a DNA oligonucleotide that forms two different i-motif structures depending on pH and temperature. At neutral pH, the major structure is stabilized by C:C+ base pairs and G:C:G:C tetrads. At pH 5, a more elongated i-motif structure with C:C+ base pairs and G:T:G:T tetrads is observed. Molecular dynamics calculations showed that the conformational transition between the two structures is driven by the protonation state of key cytosines. This study reveals the pH-dependent plasticity and conformational switch of i-motif structures.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Medicinal
Federica Battistini, Alba Sala, Adam Hospital, Modesto Orozco
Summary: The properties of DNA duplex have been accurately described using molecular dynamics simulations, but there lacks equivalent simulations for RNA duplex which is usually represented as a rigid rod. In this study, a massive simulation effort was conducted to derive the properties of RNA duplex and a simplified model for long RNA duplexes. Despite high chemical similarity, the local and global elastic properties of DNA and RNA duplexes are significantly different. Statement about the relative flexibility or stability of both polymers is meaningless and a detailed description depending on the sequence and deformation type should be used.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Israel Serrano-Chacon, Bartomeu Mir, Lorenzo Cupellini, Francesco Colizzi, Modesto Orozco, Nu'ria Escaja, Carlos Gonzalez
Summary: We studied a DNA oligonucleotide that can form two different i-motif structures, with their stability depending on pH and temperature. The structure at neutral pH is stabilized by C:C+ base pairs and G:C:G:C tetrads. At pH 5, a more elongated structure consisting of C:C+ base pairs and G:T:G:T tetrads is observed. The transition between these two structures is driven by the protonation state of key cytosines.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Juan Aranda, Milosz Wieczor, Montserrat Terrazas, Isabelle Brun-Heath, Modesto Orozco
Summary: We used molecular dynamics, statistical mechanics, and hybrid quantum mechanics/molecular mechanics simulations to elucidate the replication mechanism of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Our findings showed that the viral RdRp is highly processive and has a higher catalytic rate of incorporation compared to human RNA Pol II. Furthermore, we observed that remdesivir, an antiviral nucleotide, is incorporated more slowly into the RNA than ATP, suggesting it is not a competitive inhibitor. Overall, this study provides a detailed understanding of the replication mechanism of RdRp.