Biomolecular machines transduce free energy from one form to another to fulfill many important roles inside cells, with dissipation required to achieve directed progress. We investigate how to break time-reversal symmetry at a given dissipation cost by using deterministic protocols to drive systems over sawtooth potentials, which have frequently been used to model molecular machines as ratchets. Time asymmetry increases for sawtooth potentials with higher barriers and for driving potentials of intermediate width. For systems driven over a sawtooth potential according to a protocol, we find that symmetric sawtooths maximize time asymmetry, whereas earlier work examining ratchet models of molecular machines required asymmetric sawtooth potentials to achieve directed behavior. This distinction arises because deterministically driven machines are externally provided with direction, whereas autonomous machines must generate directed behavior.
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http://dx.doi.org/10.1103/PhysRevE.99.062127 | DOI Listing |
J Cheminform
January 2025
School of Systems Biomedical Science, Soongsil University, 369 Sangdo-ro, Dongjak-gu, 06978, Seoul, Republic of Korea.
G protein-coupled receptors (GPCRs) play vital roles in various physiological processes, making them attractive drug discovery targets. Meanwhile, deep learning techniques have revolutionized drug discovery by facilitating efficient tools for expediting the identification and optimization of ligands. However, existing models for the GPCRs often focus on single-target or a small subset of GPCRs or employ binary classification, constraining their applicability for high throughput virtual screening.
View Article and Find Full Text PDFCell Div
January 2025
Babak Myeloma Group, Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Background: Multiple myeloma (MM) represents the second most common hematological malignancy characterized by the infiltration of the bone marrow by plasma cells that produce monoclonal immunoglobulin. While the quality and length of life of MM patients have significantly increased, MM remains a hard-to-treat disease; almost all patients relapse. As MM is highly heterogenous, patients relapse at different times.
View Article and Find Full Text PDFBMC Pharmacol Toxicol
January 2025
Yanzhou District People's Hospital, Jining, Shandong, China.
Background: Osteoporosis (OP), often termed the "silent epidemic," poses a substantial public health burden. Emerging insights into the molecular functions of FBXW4 have spurred interest in its potential roles across various diseases.
Methods: This study explored FBXW4 by integrating DEGs from GEO datasets GSE2208, GSE7158, GSE56815, and GSE35956 with immune-related gene compilations from the ImmPort repository.
Nat Biotechnol
January 2025
Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Therapeutic efficacy and safety of adeno-associated virus (AAV) liver gene therapy depend on capsid choice. To predict AAV capsid performance under near-clinical conditions, we established side-by-side comparison at single-cell resolution in human livers maintained by normothermic machine perfusion. AAV-LK03 transduced hepatocytes much more efficiently and specifically than AAV5, AAV8 and AAV6, which are most commonly used clinically, and AAV-NP59, which is better at transducing human hepatocytes engrafted in immune-deficient mice.
View Article and Find Full Text PDFNature
January 2025
Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland.
During normal cellular homeostasis, unfolded and mislocalized proteins are recognized and removed, preventing the build-up of toxic byproducts. When protein homeostasis is perturbed during ageing, neurodegeneration or cellular stress, proteins can accumulate several forms of chemical damage through reactive metabolites. Such modifications have been proposed to trigger the selective removal of chemically marked proteins; however, identifying modifications that are sufficient to induce protein degradation has remained challenging.
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