Sterics and solvation winnow accessible conformational space for unfolded proteins

Nicholas C. Fitzkee, George D Rose

Research output: Contribution to journalArticle

Abstract

The magnitude of protein conformational space is over-estimated by the traditional random-coil model, in which local steric restrictions arise exclusively from interactions between adjacent chain neighbors. Using a five-state model, we assessed the extent to which steric hindrance and hydrogen bond satisfaction, energetically significant factors, impose additional conformational restrictions on polypeptide chains, beyond adjacent residues. Steric hindrance is repulsive: the distance of closest approach between any two atoms cannot be less than the sum of their van der Waals radii. Hydrogen bond satisfaction is attractive: polar backbone atoms must form hydrogen bonds, either intramolecularly or to solvent water. To gauge the impact of these two factors on the magnitude of conformational space, we systematically enumerated and classified the disfavored conformations that restrict short polyalanyl backbone chains. Applying such restrictions to longer chains, we derived a scaling law to estimate conformational restriction as a function of chain length. Disfavored conformations predicted by the model were tested against experimentally determined structures in the coil library, a non-helix, non-strand subset of the PDB. These disfavored conformations are usually absent from the coil library, and exceptions can be uniformly rationalized.

Original languageEnglish (US)
Pages (from-to)873-887
Number of pages15
JournalJournal of Molecular Biology
Volume353
Issue number4
DOIs
StatePublished - Nov 4 2005

Fingerprint

Protein Unfolding
Hydrogen
Libraries
Peptides
Water
Proteins

Keywords

  • Hydrogen-bonding
  • Protein folding
  • Random coil
  • Steric restrictions
  • Unfolded state

ASJC Scopus subject areas

  • Virology

Cite this

Sterics and solvation winnow accessible conformational space for unfolded proteins. / Fitzkee, Nicholas C.; Rose, George D.

In: Journal of Molecular Biology, Vol. 353, No. 4, 04.11.2005, p. 873-887.

Research output: Contribution to journalArticle

@article{5bc3e9dc761840f28b2d075ce8be0a85,
title = "Sterics and solvation winnow accessible conformational space for unfolded proteins",
abstract = "The magnitude of protein conformational space is over-estimated by the traditional random-coil model, in which local steric restrictions arise exclusively from interactions between adjacent chain neighbors. Using a five-state model, we assessed the extent to which steric hindrance and hydrogen bond satisfaction, energetically significant factors, impose additional conformational restrictions on polypeptide chains, beyond adjacent residues. Steric hindrance is repulsive: the distance of closest approach between any two atoms cannot be less than the sum of their van der Waals radii. Hydrogen bond satisfaction is attractive: polar backbone atoms must form hydrogen bonds, either intramolecularly or to solvent water. To gauge the impact of these two factors on the magnitude of conformational space, we systematically enumerated and classified the disfavored conformations that restrict short polyalanyl backbone chains. Applying such restrictions to longer chains, we derived a scaling law to estimate conformational restriction as a function of chain length. Disfavored conformations predicted by the model were tested against experimentally determined structures in the coil library, a non-helix, non-strand subset of the PDB. These disfavored conformations are usually absent from the coil library, and exceptions can be uniformly rationalized.",
keywords = "Hydrogen-bonding, Protein folding, Random coil, Steric restrictions, Unfolded state",
author = "Fitzkee, {Nicholas C.} and Rose, {George D}",
year = "2005",
month = "11",
day = "4",
doi = "10.1016/j.jmb.2005.08.062",
language = "English (US)",
volume = "353",
pages = "873--887",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - Sterics and solvation winnow accessible conformational space for unfolded proteins

AU - Fitzkee, Nicholas C.

AU - Rose, George D

PY - 2005/11/4

Y1 - 2005/11/4

N2 - The magnitude of protein conformational space is over-estimated by the traditional random-coil model, in which local steric restrictions arise exclusively from interactions between adjacent chain neighbors. Using a five-state model, we assessed the extent to which steric hindrance and hydrogen bond satisfaction, energetically significant factors, impose additional conformational restrictions on polypeptide chains, beyond adjacent residues. Steric hindrance is repulsive: the distance of closest approach between any two atoms cannot be less than the sum of their van der Waals radii. Hydrogen bond satisfaction is attractive: polar backbone atoms must form hydrogen bonds, either intramolecularly or to solvent water. To gauge the impact of these two factors on the magnitude of conformational space, we systematically enumerated and classified the disfavored conformations that restrict short polyalanyl backbone chains. Applying such restrictions to longer chains, we derived a scaling law to estimate conformational restriction as a function of chain length. Disfavored conformations predicted by the model were tested against experimentally determined structures in the coil library, a non-helix, non-strand subset of the PDB. These disfavored conformations are usually absent from the coil library, and exceptions can be uniformly rationalized.

AB - The magnitude of protein conformational space is over-estimated by the traditional random-coil model, in which local steric restrictions arise exclusively from interactions between adjacent chain neighbors. Using a five-state model, we assessed the extent to which steric hindrance and hydrogen bond satisfaction, energetically significant factors, impose additional conformational restrictions on polypeptide chains, beyond adjacent residues. Steric hindrance is repulsive: the distance of closest approach between any two atoms cannot be less than the sum of their van der Waals radii. Hydrogen bond satisfaction is attractive: polar backbone atoms must form hydrogen bonds, either intramolecularly or to solvent water. To gauge the impact of these two factors on the magnitude of conformational space, we systematically enumerated and classified the disfavored conformations that restrict short polyalanyl backbone chains. Applying such restrictions to longer chains, we derived a scaling law to estimate conformational restriction as a function of chain length. Disfavored conformations predicted by the model were tested against experimentally determined structures in the coil library, a non-helix, non-strand subset of the PDB. These disfavored conformations are usually absent from the coil library, and exceptions can be uniformly rationalized.

KW - Hydrogen-bonding

KW - Protein folding

KW - Random coil

KW - Steric restrictions

KW - Unfolded state

UR - http://www.scopus.com/inward/record.url?scp=26844480393&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=26844480393&partnerID=8YFLogxK

U2 - 10.1016/j.jmb.2005.08.062

DO - 10.1016/j.jmb.2005.08.062

M3 - Article

C2 - 16185713

AN - SCOPUS:26844480393

VL - 353

SP - 873

EP - 887

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 4

ER -