Flexibility and packing in proteins
(2002) In Proceedings of the National Academy of Sciences 99(3). p.1274-1279- Abstract
- Structural flexibility is an essential attribute, without which few proteins could carry out their biological functions. Much information about protein flexibility has come from x-ray crystallography, in the form of atomic mean-square displacements (AMSDs) or B factors. Profiles showing the AMSD variation along the polypeptide chain are usually interpreted in dynamical terms but are ultimately governed by the local features of a highly complex energy landscape. Here, we bypass this complexity by showing that the AMSD profile is essentially determined by spatial variations in local packing density. On the basis of elementary statistical mechanics and generic features of atomic distributions in proteins, we predict a direct inverse... (More)
- Structural flexibility is an essential attribute, without which few proteins could carry out their biological functions. Much information about protein flexibility has come from x-ray crystallography, in the form of atomic mean-square displacements (AMSDs) or B factors. Profiles showing the AMSD variation along the polypeptide chain are usually interpreted in dynamical terms but are ultimately governed by the local features of a highly complex energy landscape. Here, we bypass this complexity by showing that the AMSD profile is essentially determined by spatial variations in local packing density. On the basis of elementary statistical mechanics and generic features of atomic distributions in proteins, we predict a direct inverse proportionality between the AMSD and the contact density, i.e., the number of noncovalent neighbor atoms within a local region of approximately 1.5 nm(3) volume. Testing this local density model against a set of high-quality crystal structures of 38 nonhomologous proteins, we find that it accurately and consistently reproduces the prominent peaks in the AMSD profile and even captures minor features, such as the periodic AMSD variation within alpha helices. The predicted rigidifying effect of crystal contacts also agrees with experimental data. With regard to accuracy and computational efficiency, the model is clearly superior to its predecessors. The quantitative link between flexibility and packing density found here implies that AMSDs provide little independent information beyond that contained in the mean atomic coordinates. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/106301
- author
- Halle, Bertil LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Proceedings of the National Academy of Sciences
- volume
- 99
- issue
- 3
- pages
- 1274 - 1279
- publisher
- National Academy of Sciences
- external identifiers
-
- wos:000173752500034
- pmid:11818549
- scopus:0037022347
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.032522499
- language
- English
- LU publication?
- yes
- id
- 1e65dfa1-83f7-4706-bbab-f97e22dbba54 (old id 106301)
- date added to LUP
- 2016-04-04 08:52:55
- date last changed
- 2022-01-29 07:28:00
@article{1e65dfa1-83f7-4706-bbab-f97e22dbba54,
abstract = {{Structural flexibility is an essential attribute, without which few proteins could carry out their biological functions. Much information about protein flexibility has come from x-ray crystallography, in the form of atomic mean-square displacements (AMSDs) or B factors. Profiles showing the AMSD variation along the polypeptide chain are usually interpreted in dynamical terms but are ultimately governed by the local features of a highly complex energy landscape. Here, we bypass this complexity by showing that the AMSD profile is essentially determined by spatial variations in local packing density. On the basis of elementary statistical mechanics and generic features of atomic distributions in proteins, we predict a direct inverse proportionality between the AMSD and the contact density, i.e., the number of noncovalent neighbor atoms within a local region of approximately 1.5 nm(3) volume. Testing this local density model against a set of high-quality crystal structures of 38 nonhomologous proteins, we find that it accurately and consistently reproduces the prominent peaks in the AMSD profile and even captures minor features, such as the periodic AMSD variation within alpha helices. The predicted rigidifying effect of crystal contacts also agrees with experimental data. With regard to accuracy and computational efficiency, the model is clearly superior to its predecessors. The quantitative link between flexibility and packing density found here implies that AMSDs provide little independent information beyond that contained in the mean atomic coordinates.}},
author = {{Halle, Bertil}},
issn = {{1091-6490}},
language = {{eng}},
number = {{3}},
pages = {{1274--1279}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences}},
title = {{Flexibility and packing in proteins}},
url = {{http://dx.doi.org/10.1073/pnas.032522499}},
doi = {{10.1073/pnas.032522499}},
volume = {{99}},
year = {{2002}},
}