Article
Multidisciplinary Sciences
Markus Schneider, Iris Antes
Summary: The study introduces a new protein structure network analysis framework SenseNet, which evaluates interaction timelines obtained by molecular dynamics simulations. The results show high accuracy in predicting allosteric residues in proteins, which is important for drug design research.
Review
Biochemistry & Molecular Biology
Mengrong Li, Yiqiong Bao, Miaomiao Li, Jingjing Guo
Summary: G protein-coupled receptors (GPCRs), as a large superfamily of cell-surface proteins, play crucial roles in cell signaling and regulate various physiological and pathological processes, making them an important source of drug targets. However, due to the challenging dynamic structures of GPCRs, only a few allosteric ligands have been approved as drugs. Fortunately, the development of computational biology provides insights into the mechanism of GPCR allosteric ligands, which is vital for the discovery of new therapeutic agents. This article provides a comprehensive overview of the resources and approaches in computational biology related to GPCR allostery and conformational dynamics, as well as the current limitations and challenges in the field.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Applied
Heidi Klem, Martin McCullagh, Robert S. Paton
Summary: Understanding enzymatic mechanisms is crucial for biologics development and enzyme design; Quantum mechanical potentials aid in studying complex enzymatic mechanisms; Dynamic interconversion of enzyme conformations poses challenges for computational models; Structural clustering bridges molecular dynamics and catalysis models effectively.
TOPICS IN CATALYSIS
(2022)
Article
Chemistry, Medicinal
Dong-Gun Kim, Yoonjoo Choi, Hak-Sung Kim
Summary: The preference for a binding site by protein binders is strongly related to the structural flexibility of a target protein surface, and the relatedness of epitopes to the structural flexibility of a target protein surface is dependent on the secondary structure elements of paratopes. Monobody and repebody, whose binding sites are composed of beta-strands, distinctively prefer to bind to a relatively more rigid region of a target protein.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Engineering, Marine
Karen B. Burgaard, Stefan Carstensen, David R. Fuhrman, Bjarke E. Larsen, Finbarr G. O'Neill
Summary: An experimental and numerical study was conducted to investigate the flow behavior upstream and downstream of a disc-attached cylinder near a wall. The experimental results showed that the mean flow could be considered two-dimensional at a distance greater than the diameter of the cylinder. Both the experimental and numerical simulations found an increase in the peak amplitudes of the power spectra of vertical velocity fluctuations at a distance of 3.75 times the diameter from the centerline of the disc, caused by vortices transported by a transverse flow related to the disc.
Article
Neurosciences
Sajitha Somasundaran Nair, Mini Maniyelil Govindankutty, Minimol Balakrishnan, Krishna Prasad, Talakad N. Sathyaprabha, Kaviraja Udupa
Summary: This study investigates the occurrence patterns and severity of autonomic dysfunction in Alzheimer's disease (AD) by using a computational model to simulate heart rate variability (HRV) for different autonomic states. The results show significant changes in HRV parameters in AD patients, indicating that autonomic function assessment can aid in the diagnosis and assessment of AD.
Article
Neurosciences
Stefania Scarsoglio, Luca Ridolfi
Summary: The study utilized a computational approach to investigate the impact of HRV on deep cerebral and central hemodynamics in young healthy individuals. The results showed that HRV has a stronger impact on pressure than on flow rate mean values, with increased HRV leading to a higher probability of altered values at distal cerebral levels. Furthermore, decreased HRV was found to increase cardiac effort without improving heart efficiency.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Neurosciences
Zhenxing Hu, Zhiguo Zhang, Zhen Liang, Li Zhang, Linling Li, Gan Huang
Summary: This study rigorously evaluated the test-retest reliability of ERPs in a multisensory and cognitive experiment involving 82 healthy adolescents. It found that a stronger group-level response in ERPs did not guarantee higher individual reliability. The consistency between group-level ERP responses and individual reliability was influenced by inter-subject latency jitter and inter-trial variability. These findings suggest the need to consider a neural oscillation perspective when assessing the reliability of ERPs.
Article
Engineering, Chemical
Aldo Benavides-Moran, Luis Rodriguez-Jaime, Santiago Lain
Summary: This paper presents computational fluid dynamics simulations of a horizontal axis hydrokinetic turbine. The results show that the power and thrust coefficients decrease when the rotor is closer to the free surface, due to the slow wake recovery caused by the proximity of the shallow rotor immersion to the free surface, which in turn reduces the power extraction.
Article
Dermatology
Shinya Kondo, Takeshi Tohgasaki, Soichiro Shiga, Shino Nishizawa, Shioji Ishiwatari, Shinsuke Ishikawa, Akira Takeda, Tetsuhito Sakurai
Summary: Through a new assessment strategy, this study observed that EMILIN-1 and CTSK are closely related to changes in elastic fiber structure with aging. These results suggest that inhibiting CTSK expression and increasing EMILIN-1 expression may be an effective approach to prevent morphological changes in elastic fibers that lead to wrinkles and sagging. Additionally, the increase of EMILIN-1 in the dermis due to interaction with the epidermis could offer a new target for therapeutic care of elastic fibers in epidermis-dermis interaction.
JOURNAL OF COSMETIC DERMATOLOGY
(2022)
Article
Clinical Neurology
Lin Li, Zili Liu, Haiyang Yang, Yang Li, Qi Zeng, Li Chen, Yidi Liu, Yan Chen, Fengjun Zhu, Dezhi Cao, Jun Hu, Xuefeng Shen
Summary: This study identified two novel KCNC2 variants in patients with early onset developmental and epileptic encephalopathy, providing evidence supporting the role of KCNC2 as a disease-causing gene in human neurodevelopmental delay and epilepsy.
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
(2022)
Article
Environmental Sciences
Wanzhou Wang, Wenlou Zhang, Luyi Li, Dayu Hu, Shan Liu, Liyan Cui, Junxiu Liu, Junhui Xu, Xinbiao Guo, Furong Deng
Summary: Research has found that obese individuals are more susceptible to the detrimental effects of environmental noise on heart rate variability. Abnormal levels of blood pressure, glucose and lipid metabolism, and inflammatory indicators may explain this association.
ENVIRONMENTAL POLLUTION
(2023)
Article
Computer Science, Theory & Methods
Mourad Baiou, Rafael Colares, Herve Kerivin
Summary: This paper discusses the Stop Number Problem in a dial-a-ride system served by an autonomous electric vehicle fleet. The authors show the problem's relation to other known problems and provide a complexity analysis. The research findings are significant for optimizing fleet management.
THEORETICAL COMPUTER SCIENCE
(2022)
Article
Psychology, Clinical
Andrea Sandstrom, Adam S. Radomsky
Summary: This study found a link between beliefs about losing control and OCD-relevant appraisals, although the direction of the effect was opposite to what was hypothesized in the aggressive thoughts context.
JOURNAL OF BEHAVIOR THERAPY AND EXPERIMENTAL PSYCHIATRY
(2024)
Article
Biochemistry & Molecular Biology
Changwei Shen, Jingping Yuan
Summary: In this study, 44 putative K+ transport-related genes were identified in Chinese cabbage, including both uptake permease and channel genes. Phylogenetic analysis revealed that these genes could be classified into five clades and exhibited conserved exon-intron distributions and motif compositions. The uneven distribution of these genes across all ten chromosomes and tissue-specific expression patterns were observed, with higher expression levels of KUP/HAK/KT genes compared to potassium channel genes in six tissues. Promoter analysis suggested potential associations with responses to various abiotic stresses.
BIOCHEMICAL GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Andreas Porodko, Ana Cirnski, Drazen Petrov, Teresa Raab, Melanie Paireder, Bettina Mayer, Daniel Maresch, Lisa Nika, Martin L. Biniossek, Patrick Gallois, Oliver Schilling, Chris Oostenbrink, Marko Novinec, Lukas Mach
BIOLOGICAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Nejc Petek, Bogdan Stefane, Marko Novinec, Jurij Svete
BIOORGANIC CHEMISTRY
(2019)
Article
Biochemical Research Methods
Mateja Rebernik, Brigita Lenarcic, Marko Novinec
PROTEIN EXPRESSION AND PURIFICATION
(2019)
Article
Biochemistry & Molecular Biology
Nika Strasek, Lara Lavrencic, Andraz Ostrek, Dejan Slapsak, Uros Groselj, Marina Klemencic, Helena Brodnik Zugelj, Jernej Wagger, Marko Novinec, Jurij Svete
BIOORGANIC CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Mateja Rebernik, Tina Snoj, Marina Klemencic, Marko Novinec
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2019)
Article
Biochemistry & Molecular Biology
Liza Ulcakar, Marko Novinec
Summary: CA, CAPE, and CGA were found to inhibit cathepsins B and L, with CA showing the strongest inhibition against cathepsin B. These compounds act as linear inhibitors through mixed or catalytic mechanisms, and display differing levels of inhibition at different pH values.
Article
Biochemistry & Molecular Biology
Tjasa Gorican, Luka Ciber, Nejc Petek, Jurij Svete, Marko Novinec
Summary: Cathepsins K and S are closely related papain-like cysteine peptidases, potential therapeutic targets for metabolic and inflammatory diseases. In this study, a new hyperbolic inhibitor of cathepsin K and the potential of succinimide scaffold as inhibitors of cathepsins K and S were investigated. Small molecules hyperbolic inhibitors of cathepsin S were identified, which will be further explored for potential inhibition of cysteine cathepsins in in vitro models.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Zala Zivic, Ziga Strmsek, Marko Novinec, Jurij Lah, San Hadzi
Summary: The spike trimer of SARS-CoV-2 plays a crucial role in infection and vaccine development. In this study, the researchers characterized the structure and thermodynamic stability of the stalk domain of the spike trimer. They found that the N-terminal segment of the stalk remains disordered, while the C-terminal segment forms a stable trimeric coiled-coil. The crystal structure of the stalk segment revealed a novel tetramer coiled-coil with an unusual hydrophobic core packing. This study highlights the highly polymorphic nature of the SARS-CoV-2 spike stalk sequence.
Article
Biochemistry & Molecular Biology
Nina Varda, Marko Novinec
Summary: The aim of this study was to investigate the evolution of DPPI and reconstruct the evolution of its oligomerization. The results showed that the oligomeric state of DPPI varies between different lineages, and the dependence on chloride ions for enzymatic activity is an evolutionarily conserved feature of DPPI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Marko Novinec, Primoz Bembic, Milica Jankovic, Marija Kisilak, Jakob Kljun, Iztok Turel
Summary: Heavy metal ions, such as gallium and cerium, can inhibit the activity of human papain-like cysteine endopeptidases, while zinc and lead ions are known inhibitors of thiol enzymes. The inhibition constants of Ga3+, Ce3+, and Ce4+ ions are comparable to Zn2+ ions, indicating their potential as cysteine cathepsin inhibitors. These ions also inhibit the degradation of elastin, suggesting their possible application in treating inflammatory diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Luka Vah, Tadej Medved, Uros Groselj, Marina Klemencic, Crtomir Podlipnik, Bogdan Stefane, Jernej Wagger, Marko Novinec, Jurij Svete
Summary: In silico evaluation showed that regioisomeric 5- and 3-hydroxy-substituted alkyl 1-aryl-1H-pyrazole-4-carboxylates have promising binding capability in the active site of dihydroorotate dehydrogenase of Plasmodium falciparum. Four ethyl 1-aryl-5-hydroxy-1H-pyrazole-4-carboxylates and their 3-hydroxy regioisomers were successfully prepared. Testing the compounds for their inhibition of PfDHODH revealed that some of them exhibited higher potency than a known inhibitor.
Article
Chemistry, Multidisciplinary
Andrea Geri, Lara Massai, Marko Novinec, Iztok Turel, Luigi Messori
Summary: Medicinal gold compounds exert their pharmacological effects by binding to protein targets. In this study, the reactions between seven representative gold compounds and the cysteine protease cathepsin B were explored, revealing strong interactions with the free cysteine in the enzyme. The findings suggest that the chemical nature of the gold compound plays a significant role in its interaction with proteins.
Article
Chemistry, Multidisciplinary
Branislav Lukic, Uros Groselj, Marko Novinec, Jurij Svete
ACTA CHIMICA SLOVENICA
(2017)
Article
Biochemistry & Molecular Biology
Melanie Paireder, Stefan Tholen, Andreas Porodko, Martin L. Biniossek, Bettina Mayer, Marko Novinec, Oliver Schilling, Lukas Mach
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2017)
Article
Biochemistry & Molecular Biology
Vashendriya V. V. Hira, Urska Verbovsek, Barbara Breznik, Matic Srdic, Marko Novinec, Hala Kakar, Jill Wormer, Britt Van der Swaan, Brigita Lenarcic, Luiz Juliano, Shwetal Mehta, Cornelis J. F. Van Noorden, Tamara T. Lah
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2017)