Computer simulations of protein translocation

Serdal Kirmizialtin, Lei Huang, Dmitrii E. Makarov

Research output: Contribution to journalArticle

Abstract

Many biological processes, e.g. protein degradation by ATP dependent proteases and mitochondrial protein import, involve protein translocation through nanometer-sized pores. In this paper, we report on computer simulations of two models of protein translocation. In the first model, a protein domain is pulled mechanically through a narrow neutral pore. We compare the free energy cost of squeezing an initially folded protein into the pore with that for a random-coil-like homopolymer and show that the former case involves several partially folded intermediates. The second model involves electrophoretically driven translocation of a β-hairpin forming peptide across the α-hemolysin protein pore. The distribution of the time the peptide spends inside the pore is exponential at low forces, suggesting a single rate limiting barrier crossing step for the translocation process, while at higher forces this distribution tends to be a bell shaped curve. The dependence of the average translocation time 〈t〉 on the applied force f is well described by the exponential relationship: ln 〈t〉 = af + b at low forces, while at high forces the inverse translocation time is a linear function of the force, 〈t〉-1 = Af - B.

Original languageEnglish (US)
Pages (from-to)2038-2047
Number of pages10
JournalPhysica Status Solidi (B) Basic Research
Volume243
Issue number9
DOIs
StatePublished - Jul 1 2006

Fingerprint

computerized simulation
proteins
Proteins
Computer simulation
porosity
ATP-Dependent Proteases
Peptides
peptides
Hemolysin Proteins
Mitochondrial Proteins
Homopolymerization
force distribution
Free energy
protease
adenosine triphosphate
Adenosinetriphosphate
bells
compressing
Degradation
coils

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Condensed Matter Physics

Cite this

Computer simulations of protein translocation. / Kirmizialtin, Serdal; Huang, Lei; Makarov, Dmitrii E.

In: Physica Status Solidi (B) Basic Research, Vol. 243, No. 9, 01.07.2006, p. 2038-2047.

Research output: Contribution to journalArticle

Kirmizialtin, Serdal ; Huang, Lei ; Makarov, Dmitrii E. / Computer simulations of protein translocation. In: Physica Status Solidi (B) Basic Research. 2006 ; Vol. 243, No. 9. pp. 2038-2047.
@article{c4da95fa3f834691b6ab8b6df80fd251,
title = "Computer simulations of protein translocation",
abstract = "Many biological processes, e.g. protein degradation by ATP dependent proteases and mitochondrial protein import, involve protein translocation through nanometer-sized pores. In this paper, we report on computer simulations of two models of protein translocation. In the first model, a protein domain is pulled mechanically through a narrow neutral pore. We compare the free energy cost of squeezing an initially folded protein into the pore with that for a random-coil-like homopolymer and show that the former case involves several partially folded intermediates. The second model involves electrophoretically driven translocation of a β-hairpin forming peptide across the α-hemolysin protein pore. The distribution of the time the peptide spends inside the pore is exponential at low forces, suggesting a single rate limiting barrier crossing step for the translocation process, while at higher forces this distribution tends to be a bell shaped curve. The dependence of the average translocation time 〈t〉 on the applied force f is well described by the exponential relationship: ln 〈t〉 = af + b at low forces, while at high forces the inverse translocation time is a linear function of the force, 〈t〉-1 = Af - B.",
author = "Serdal Kirmizialtin and Lei Huang and Makarov, {Dmitrii E.}",
year = "2006",
month = "7",
day = "1",
doi = "10.1002/pssb.200666812",
language = "English (US)",
volume = "243",
pages = "2038--2047",
journal = "Physica Status Solidi (B): Basic Research",
issn = "0370-1972",
publisher = "Wiley-VCH Verlag",
number = "9",

}

TY - JOUR

T1 - Computer simulations of protein translocation

AU - Kirmizialtin, Serdal

AU - Huang, Lei

AU - Makarov, Dmitrii E.

PY - 2006/7/1

Y1 - 2006/7/1

N2 - Many biological processes, e.g. protein degradation by ATP dependent proteases and mitochondrial protein import, involve protein translocation through nanometer-sized pores. In this paper, we report on computer simulations of two models of protein translocation. In the first model, a protein domain is pulled mechanically through a narrow neutral pore. We compare the free energy cost of squeezing an initially folded protein into the pore with that for a random-coil-like homopolymer and show that the former case involves several partially folded intermediates. The second model involves electrophoretically driven translocation of a β-hairpin forming peptide across the α-hemolysin protein pore. The distribution of the time the peptide spends inside the pore is exponential at low forces, suggesting a single rate limiting barrier crossing step for the translocation process, while at higher forces this distribution tends to be a bell shaped curve. The dependence of the average translocation time 〈t〉 on the applied force f is well described by the exponential relationship: ln 〈t〉 = af + b at low forces, while at high forces the inverse translocation time is a linear function of the force, 〈t〉-1 = Af - B.

AB - Many biological processes, e.g. protein degradation by ATP dependent proteases and mitochondrial protein import, involve protein translocation through nanometer-sized pores. In this paper, we report on computer simulations of two models of protein translocation. In the first model, a protein domain is pulled mechanically through a narrow neutral pore. We compare the free energy cost of squeezing an initially folded protein into the pore with that for a random-coil-like homopolymer and show that the former case involves several partially folded intermediates. The second model involves electrophoretically driven translocation of a β-hairpin forming peptide across the α-hemolysin protein pore. The distribution of the time the peptide spends inside the pore is exponential at low forces, suggesting a single rate limiting barrier crossing step for the translocation process, while at higher forces this distribution tends to be a bell shaped curve. The dependence of the average translocation time 〈t〉 on the applied force f is well described by the exponential relationship: ln 〈t〉 = af + b at low forces, while at high forces the inverse translocation time is a linear function of the force, 〈t〉-1 = Af - B.

UR - http://www.scopus.com/inward/record.url?scp=33746407709&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746407709&partnerID=8YFLogxK

U2 - 10.1002/pssb.200666812

DO - 10.1002/pssb.200666812

M3 - Article

AN - SCOPUS:33746407709

VL - 243

SP - 2038

EP - 2047

JO - Physica Status Solidi (B): Basic Research

JF - Physica Status Solidi (B): Basic Research

SN - 0370-1972

IS - 9

ER -