Apr 22, 2020

protein-sol pKa: prediction of electrostatic frustration, with application to coronaviruses

BioRxiv : the Preprint Server for Biology
M. Hebditch, Jim Warwicker

Abstract

Evolution couples differences in ambient pH to biological function through protonatable groups, in particular those that switch from buried to exposed and alter protonation state in doing so. We present a tool focusing on structure-based discovery and display of these groups. Since prediction of buried group pKas is computationally intensive, solvent accessibility of ionisable groups is displayed, from which the user can iteratively select pKa calculation centers. Results are color-coded, with emphasis on buried groups. Utility is demonstrated with coronaviruses, which exhibit variable dependence on the acidic pH of the endocytotic pathway. After benchmarking with variants of murine hepatitis virus, a pair of conserved histidine residues are identified that are predicted to be electrostatically frustrated at acidic pH in a common structural core of pre- and post-fusion coronavirus spike proteins. We suggest that an intermediate expanded conformation at endosomal pH could relax the frustration, allowing histidine protonation, and facilitating conformational conversion. This tool is available at http://www.protein-sol.manchester.ac.uk/pka/.

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Neutralising Antibodies Analysis
Vaccines, Inactivated
Study
Nanoparticle Albumin-Bound Rapamycin
Formalin
Virus
Immunologic Adjuvants
Vaccines
Adjuvant
Aluminum potassium sulfate

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Acute viral rhinopharyngitis

Acute viral rhinopharyngitis, also known as "common cold", is an acute, self-limiting viral infection of the upper respiratory tract involving the nose, sinuses, pharynx and larynx. Discover the latest research on acute viral rhinopharyngitis here.

Avian Influenza: Innate Immune Adjuvant (ASM)

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.

Avian Influenza: Innate Immune Adjuvant

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.

Related Papers

Current Opinion in Virology
Nicholas Glanville, Sebastian L Johnston
The Journal of Infectious Diseases
Ronald B Turner
South African Medical Journal = Suid-Afrikaanse Tydskrif Vir Geneeskunde
G C Soeters
© 2020 Meta ULC. All rights reserved