Computational Insights into Avidity of Polymeric Multivalent Binders.

08:00 EDT 24th July 2019 | BioPortfolio

Summary of "Computational Insights into Avidity of Polymeric Multivalent Binders."

Multivalent binding interactions are commonly found throughout biology to enhance weak monovalent binding such as between glycoligands and protein receptors. Designing multivalent polymers to bind to viruses and toxic proteins is a promising avenue for inhibiting their attachment and subsequent infection of cells. Several studies have focused on oligomeric multivalent inhibitors and how changing parameters such as ligand shape, size, linker length, and flexibility affect binding. However, experimental studies of how larger structural parameters of multivalent polymers, such as degree of polymerization, affect binding avidity to targets have mixed results, with some finding an improvement with longer polymers and some finding no effect. Here, we use Brownian dynamics simulations to provide a theoretical understanding of how the degree of polymerization affects the binding avidity of multivalent polymers. We show that longer polymers increase binding avidity to multivalent targets but reach a limit in binding avidity at high degrees of polymerization. We also show that when interacting with multiple targets simultaneously, longer polymers are able to use intertarget interactions to promote clustering and improve binding efficiency. We expect our results to narrow the design space for optimizing the structure and effectiveness of multivalent inhibitors as well as be useful to understand biological design strategies for multivalent binding.


Journal Details

This article was published in the following journal.

Name: Biophysical journal
ISSN: 1542-0086


DeepDyve research library

PubMed Articles [4687 Associated PubMed Articles listed on BioPortfolio]

Linker Dependence of Avidity in Multivalent Interactions between Disordered Proteins.

Multidomain proteins often interact through several independent binding sites connected by disordered linkers. The architecture of such linkers affect avidity by modulating the effective concentration...

Stiffness can mediate balance between hydrodynamic forces and avidity to impact the targeting of flexible polymeric nanoparticles in flow.

We report computational investigations of deformable polymeric nanoparticles (NPs) under colloidal suspension flow and adhesive environment. We employ a coarse-grained model for the polymeric NP and p...

Multivalent Interactions of Polyamide Based Sequence-Controlled Glycomacromolecules with Concanavalin A.

Binding of mannose presenting macromolecules to the protein receptor concanavalin A (ConA) is investigated by means of single-molecule atomic force spectroscopy (SMFS) in combination with dynamic ligh...

Identifying efficient toxin A binders with a multivalent neo-glycoprotein glycan library.

infections cause gastrointestinal disorders and can lead to life-threatening conditions. The symp-toms can vary from severe diarrhea to the formation of pseudomembranous colitis and therefore trigger ...

Evaluation of a BioRad Avidity assay for identification of recent HIV-1 infections using dried serum or plasma spots.

Serological methods to differentiate between recently acquired and established HIV-1 infections are a useful tool in the HIV-surveillance to characterize the epidemic, identify groups at risk and asse...

Clinical Trials [387 Associated Clinical Trials listed on BioPortfolio]

Trial to Evaluate the Safety and Immunogenicity of Multivalent Pneumococcal Vaccines in Japanese Adults 18 to 49 Years of Age.

This Phase 1b will describe the safety and immunogenicity of 2 multivalent pneumococcal conjugate vaccine formulations in healthy Japanese adults in the United States.

Study to Evaluate the Safety and Immunogenicity of a Multivalent Pneumococcal Vaccine Given With Prevnar 13 in Healthy Infants

This is a Phase 2, randomized, active-controlled, open-label study with a 3-arm parallel design. Healthy 2-month old infants (42 to 98 days of age) with no history of pneumococcal vaccinat...

Evaluation of a Polymeric Plate Derived From Castor Oil to Thermotherapy

The objective of this work is to evaluate, from volunteers viewpoint, the usability, comfort, appearance, weight, superficial temperature, and other characteristics of a polymeric plate de...

Clinical Outcomes With Electroconvulsive Therapy: Insights From Computational Modelling

This study will generate new information on how to optimise brain targets with ECT stimulation.

Trial to Evaluate the Safety and Immunogenicity of a Multivalent Pneumococcal Vaccine in Healthy Infants

A Phase 2, Randomized, Double-Blind Trial to Evaluate the Safety and Immunogenicity of a Multivalent Pneumococcal Conjugate Vaccine in Healthy Infants

Medical and Biotech [MESH] Definitions

A 15 kD "joining" peptide that forms one of the linkages between monomers of IMMUNOGLOBULIN A or IMMUNOGLOBULIN M in the formation of polymeric immunoglobulins. There is one J chain per one IgA dimer or one IgM pentamer. It is also involved in binding the polymeric immunoglobulins to POLYMERIC IMMUNOGLOBULIN RECEPTOR which is necessary for their transcytosis to the lumen. It is distinguished from the IMMUNOGLOBULIN JOINING REGION which is part of the IMMUNOGLOBULIN VARIABLE REGION of the immunoglobulin light and heavy chains.

Specialized Fc receptors (RECEPTORS, FC) for polymeric immunoglobulins, which mediate transcytosis of polymeric IMMUNOGLOBULIN A and IMMUNOGLOBULIN M into external secretions. They are found on the surfaces of epithelial cells and hepatocytes. After binding to IMMUNOGLOBULIN A, the receptor-ligand complex undergoes endocytosis, transport by vesicle, and secretion into the lumen by exocytosis. Before release, the part of the receptor (SECRETORY COMPONENT) that is bound to IMMUNOGLOBULIN A is proteolytically cleaved from its transmembrane tail. (From Rosen et al., The Dictionary of Immunology, 1989)

Polymeric materials (usually organic) of large molecular weight which can be shaped by flow. Plastic usually refers to the final product with fillers, plasticizers, pigments, and stabilizers included (versus the resin, the homogeneous polymeric starting material). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)

Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form. These include binders, matrix, base or diluent in pills, tablets, creams, salves, etc.

Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).

Quick Search

DeepDyve research library

Relevant Topics

Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...

Biological Therapy
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...

Searches Linking to this Article