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PreprintCited by 4Protein Structure and DynamicsComputational Drug Discovery MethodsNanoparticle-Based Drug Delivery

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Statistical Survey of Chemical and Geometric Patterns on Protein Surfaces as a Blueprint for Protein-mimicking Nanoparticles

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McBride, John M., Koshevarnikov, Aleksei, Siek, Marta, Grzybowski, Bartosz A., Tlusty, Tsvi·2024·Small Structures
DOI 10.1101/2024.07.18.604221

Preprint — published as 10.1002/sstr.202400086

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Abstract

Despite recent breakthroughs in understanding how protein sequence relates to structure and function, considerably less attention has been paid to the general features of protein surfaces beyond those regions involved in binding and catalysis. This paper provides a systematic survey of the universe of protein surfaces and quantifies the sizes, shapes, and curvatures of the positively/negatively charged and hydrophobic/hydrophilic surface patches as well as correlations between such patches. It then compares these statistics with the metrics characterizing nanoparticles functionalized with ligands terminated with positively and negatively charged ligands. These particles are of particular interest because they are also surface-patchy and have been shown to exhibit both antibiotic and anticancer activities – via selective interactions against various cellular structures – prompting loose analogies to proteins. Our analyses support such analogies in several respects (e.g., patterns of charged protrusions and hydrophobic niches similar to those observed in proteins), although there are also significant differences. Looking forward, this work provides a blueprint for the rational design of synthetic nanoobjects with further enhanced mimicry of proteins’ surface properties.

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Metadata

Authors
McBride, J. M., Koshevarnikov, A., Siek, M., Grzybowski, B. A., & Tlusty, T.
Affiliations
  • Institute for Basic Science (KR)
  • Institute of Organic Chemistry (PL)
Corresponding author
  • McBride, John M.
  • Grzybowski, Bartosz A.
  • Tlusty, Tsvi
ORCID
Venue
Small Structures
Publisher
openRxiv
Published
2024-07-19
Volume
5
Issue
9
ISSN
2688-4062 (ISSN-L)
DOI
10.1101/2024.07.18.604221
OpenAlex
W4401870761
Cited by
4
References
1
Citations by year
2026: 1 · 2025: 3
FWCI
0.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Small Structures (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • arXiv (Cornell University) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • arXiv (Cornell University)
Funders
  • Korea Basic Science Institute (IBS-R020)
  • Institute for Basic Science (IBS-R-020, IBS-R-020-D1, R020-D1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
protein surface, surface patches, hydrophobic patch, surface curvature, nanoparticle functionalization, ligand-functionalized nanoparticles, antibiotic activity, anticancer activity

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