---
_id: '4017'
abstract:
- lang: eng
text: Identification and size characterization of surface pockets and occluded cavities
are initial steps in protein structure-based ligand design. A new program, CAST,
for automatically locating and measuring protein pockets and cavities, is based
on precise computational geometry methods, including alpha shape and discrete
flow theory. CAST identifies and measures pockets and pocket mouth openings, as
well as cavities. The program specifies the atoms lining pockets, pocket openings.
and buried cavities; the volume and area of pockets and cavities; and the area
and circumference of mouth openings. CAST analysis of over 100 proteins has been
carried out; proteins examined include a set of 51 monomeric enzyme-ligand structures,
several elastase-inhibitor complexes, the FK506 binding protein, 30 HIV-1 protease-inhibitor
complexes, and a number of small and large protein inhibitors, Medium-sized globular
proteins typically have 10-20 pockets/cavities. Most often, binding sites are
pockets with 1-2 mouth openings; much less frequently they are cavities. Ligand
binding pockets vary widely in size, most within the range 10(2)-10(3) Angstrom(3).
Statistical analysis reveals that the number of pockets and cavities is correlated
with protein size, but there is no correlation between the size of the protein
and the size of binding sites. Most frequently, the largest pocket/cavity is thp
active site, but there are a number of instructive exceptions. Ligand volume and
binding site volume are somewhat correlated when binding site volume is less than
or equal to 700 Angstrom(3), but the ligand seldom occupies the entire site. Auxiliary
pockets near the active site have been suggested as additional binding surface
for designed ligands (Mattos C ct al., 1993, Nat Struct Biol 1:55-58). Analysis
of elastase-inhibitor complexes suggests that CAST can identify ancillary pockets,
suitable for recruitment in ligand design strategies. Analysis of the FK506 binding
protein, and of compounds developed in SAR by NMR (Shuker SE et al.. 1996, Science
274:1531-1534), indicates that CAST pocket computation may provide a priori identification
of target proteins for Linked-fragment design. CAST analysis of 30 HIV-1 protease-inhibitor
complexes shows that the flexible active site pocket can vary over a range of
853-1,566 Angstrom(3), and that there are two pockets near or adjoining the active
site that may be recruited for ligand design.
article_processing_charge: No
article_type: original
author:
- first_name: Jie
full_name: Liang, Jie
last_name: Liang
- first_name: Herbert
full_name: Edelsbrunner, Herbert
id: 3FB178DA-F248-11E8-B48F-1D18A9856A87
last_name: Edelsbrunner
orcid: 0000-0002-9823-6833
- first_name: Clare
full_name: Woodward, Clare
last_name: Woodward
citation:
ama: 'Liang J, Edelsbrunner H, Woodward C. Anatomy of protein pockets and cavities:
Measurement of binding site geometry and implications for ligand design. Protein
Science. 1998;7(9):1884-1897. doi:10.1002/pro.5560070905'
apa: 'Liang, J., Edelsbrunner, H., & Woodward, C. (1998). Anatomy of protein
pockets and cavities: Measurement of binding site geometry and implications for
ligand design. Protein Science. Wiley-Blackwell. https://doi.org/10.1002/pro.5560070905'
chicago: 'Liang, Jie, Herbert Edelsbrunner, and Clare Woodward. “Anatomy of Protein
Pockets and Cavities: Measurement of Binding Site Geometry and Implications for
Ligand Design.” Protein Science. Wiley-Blackwell, 1998. https://doi.org/10.1002/pro.5560070905.'
ieee: 'J. Liang, H. Edelsbrunner, and C. Woodward, “Anatomy of protein pockets and
cavities: Measurement of binding site geometry and implications for ligand design,”
Protein Science, vol. 7, no. 9. Wiley-Blackwell, pp. 1884–1897, 1998.'
ista: 'Liang J, Edelsbrunner H, Woodward C. 1998. Anatomy of protein pockets and
cavities: Measurement of binding site geometry and implications for ligand design.
Protein Science. 7(9), 1884–1897.'
mla: 'Liang, Jie, et al. “Anatomy of Protein Pockets and Cavities: Measurement of
Binding Site Geometry and Implications for Ligand Design.” Protein Science,
vol. 7, no. 9, Wiley-Blackwell, 1998, pp. 1884–97, doi:10.1002/pro.5560070905.'
short: J. Liang, H. Edelsbrunner, C. Woodward, Protein Science 7 (1998) 1884–1897.
date_created: 2018-12-11T12:06:27Z
date_published: 1998-09-01T00:00:00Z
date_updated: 2022-08-25T12:49:41Z
day: '01'
doi: 10.1002/pro.5560070905
extern: '1'
external_id:
pmid:
- '9761470 '
intvolume: ' 7'
issue: '9'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2144175/
month: '09'
oa: 1
oa_version: Published Version
page: 1884 - 1897
pmid: 1
publication: Protein Science
publication_identifier:
issn:
- 0961-8368
publication_status: published
publisher: Wiley-Blackwell
publist_id: '2111'
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Anatomy of protein pockets and cavities: Measurement of binding site geometry
and implications for ligand design'
type: journal_article
user_id: ea97e931-d5af-11eb-85d4-e6957dddbf17
volume: 7
year: '1998'
...