Uniform description of polymer ejection dynamics from capsid with and without hydrodynamics.

Phys Rev E

Department of Computer Science, Aalto University, P. O. Box 15400, FI-00076 Aalto, Finland.

Published: May 2017

We use stochastic rotation dynamics (SRD) to examine the dynamics of the ejection of an initially strongly confined flexible polymer from a spherical capsid with and without hydrodynamics. The results obtained using stochastic rotation dynamics (SRD) are compared to similar Langevin simulations. Inclusion of hydrodynamic modes speeds up the ejection but also allows the part of the polymer outside the capsid to expand closer to equilibrium. This shows as higher values of radius of gyration when hydrodynamics are enabled. By examining the waiting times of individual polymer beads, we find that the waiting time t_{w} grows with the number of ejected monomers s as a sum of two exponents. When ≈63% of the polymer has ejected, the ejection enters the regime of slower dynamics. The functional form of t_{w} versus s is universal for all ejection processes starting from the same initial monomer densities. Inclusion of hydrodynamics only reduces its magnitude. Consequently, we define a universal scaling function h such that the cumulative waiting time t=N_{0}h(s/N_{0}) for large N_{0}. Our unprecedentedly precise measurements of force indicate that this form for t_{w}(s) originates from the corresponding force toward the pore decreasing superexponentially at the end of the ejection. Our measured t_{w}(s) explains the apparent superlinear scaling of the ejection time with the polymer length for short polymers. However, for asymptotically long polymers, t_{w}(s) predicts linear scaling.

Download full-text PDF

Source
http://dx.doi.org/10.1103/PhysRevE.95.052418DOI Listing

Publication Analysis

Top Keywords

capsid hydrodynamics
8
hydrodynamics stochastic
8
stochastic rotation
8
rotation dynamics
8
dynamics srd
8
waiting time
8
ejection
7
polymer
6
dynamics
5
uniform description
4

Similar Publications

This study investigates the effect of hydraulic shock waves on inactivation of MS-2 bacteriophage, a norovirus surrogate. A falling circular jet of water spiked with the MS-2 (∼1000 PFU/mL) was repeatedly impacted by a rotating blade, resulting in occurrence of hydraulic shock waves within the liquid region adjacent to the impact. The proof-of-concept rotational generator of hydraulic shock treating 9 L of water spiked with viruses was able to achieve 3 logs reduction of viral plaque count within 80-100 liquid passes at moderate blade impact velocities (namely, 70 and 88 m/s) despite the water temperature not exceeding 40 °C and no detectible cavitation.

View Article and Find Full Text PDF

HBV capsid assembly modulators (CAMs) target the core protein and inhibit pregenomic RNA encapsidation and viral replication. HBV CAMs also interfere with cccDNA formation during de novo infection, which in turn suppresses transcription and production of HBV antigens. In this report, we describe the antiviral activities of AB-836, a potent and highly selective HBV CAM.

View Article and Find Full Text PDF

Conformationally Constrained Isoquinolinones as Orally Efficacious Hepatitis B Capsid Assembly Modulators.

ACS Med Chem Lett

September 2024

Arbutus Biopharma, Inc., 701 Veterans Circle, Warminster, Pennsylvania 18974, United States.

Isoquinolinone-based HBV capsid assembly modulators that bind at the dimer:dimer interface of HBV core protein have been shown to suppress viral replication in chronic hepatitis B patients. Analysis of their binding mode by protein X-ray crystallography has identified a region of the small molecule where the application of a constraint can lock the preferred binding conformation and has allowed for further optimization of this class of compounds. Key analogues demonstrated single digit nM EC values in reducing HBV DNA in a HepDE19 cellular assay in addition to favorable ADME and pharmacokinetic properties, leading to a high degree of oral efficacy in a relevant hydrodynamic injection mouse model of HBV infection, with effecting a 3 log decline in serum HBV DNA levels at a once daily dose of 1 mg/kg.

View Article and Find Full Text PDF

Development of benzimidazole-based compounds as novel capsid assembly modulators for the treatment of HBV infection.

Eur J Med Chem

May 2024

Key Laboratory of Tropical Biological Resources of Ministry of Education and One Health Institute, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, China. Electronic address:

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a promising therapeutic approach for the treatment of HBV infection. In this study, the hit compound CDI (IC = 2.46 ± 0.

View Article and Find Full Text PDF
Article Synopsis
  • * A new nanoparticle named VP28-heparin was developed by conjugating heparin with an immuno-stealth protein, showcasing promising properties such as non-immunogenicity and a size that helps it evade rapid removal from circulation.
  • * In tests, VP28-heparin demonstrated improved anticoagulation effects compared to traditional heparin without negatively impacting platelet counts or causing severe side effects, making it a potentially safer therapeutic option.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!