Ligand diffusion on protein surface observed in molecular dynamics simulation

Dmitry Nerukh, Noriaki Okimoto, Atsushi Suenaga, Makoto Taiji

Research output: Contribution to journalArticle

Abstract

The process of binding of small ligands to dihydrofolate reductase protein has been investigated using all-atom molecular dynamics simulations. The existence of a mechanism that facilitates the search of the binding site by the ligand is demonstrated. The mechanism consists of ligand diffusing on the protein’s surface. It has been discussed in the literature before, but has not been explicitly confirmed for realistic molecular systems. The strength of this nonspecific binding is roughly estimated and found to be essential for the binding kinetics.
Original languageEnglish
Pages (from-to)3476–3479
Number of pages4
JournalJournal of Physical Chemistry Letters
Volume3
Issue number23
DOIs
Publication statusPublished - 6 Nov 2012

Fingerprint

Molecular dynamics
Membrane Proteins
Ligands
molecular dynamics
proteins
Proteins
ligands
Computer simulation
Tetrahydrofolate Dehydrogenase
simulation
Binding sites
Binding Sites
Atoms
Kinetics
kinetics
atoms
Oxidoreductases

Keywords

  • small ligand binding
  • protein ligand binding
  • binding rate
  • facilitated binding
  • surface diffusion
  • mycobacterium tuberculosis dihydrofolate reductase

Cite this

Nerukh, Dmitry ; Okimoto, Noriaki ; Suenaga, Atsushi ; Taiji, Makoto. / Ligand diffusion on protein surface observed in molecular dynamics simulation. In: Journal of Physical Chemistry Letters. 2012 ; Vol. 3, No. 23. pp. 3476–3479.
@article{68e312c64d1645be80525418a1d83d10,
title = "Ligand diffusion on protein surface observed in molecular dynamics simulation",
abstract = "The process of binding of small ligands to dihydrofolate reductase protein has been investigated using all-atom molecular dynamics simulations. The existence of a mechanism that facilitates the search of the binding site by the ligand is demonstrated. The mechanism consists of ligand diffusing on the protein’s surface. It has been discussed in the literature before, but has not been explicitly confirmed for realistic molecular systems. The strength of this nonspecific binding is roughly estimated and found to be essential for the binding kinetics.",
keywords = "small ligand binding, protein ligand binding, binding rate, facilitated binding, surface diffusion, mycobacterium tuberculosis dihydrofolate reductase",
author = "Dmitry Nerukh and Noriaki Okimoto and Atsushi Suenaga and Makoto Taiji",
year = "2012",
month = "11",
day = "6",
doi = "10.1021/jz301635h",
language = "English",
volume = "3",
pages = "3476–3479",
journal = "Journal of Physical Chemistry Letters",
issn = "1948-7185",
publisher = "American Chemical Society",
number = "23",

}

Ligand diffusion on protein surface observed in molecular dynamics simulation. / Nerukh, Dmitry; Okimoto, Noriaki; Suenaga, Atsushi; Taiji, Makoto.

In: Journal of Physical Chemistry Letters, Vol. 3, No. 23, 06.11.2012, p. 3476–3479.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ligand diffusion on protein surface observed in molecular dynamics simulation

AU - Nerukh, Dmitry

AU - Okimoto, Noriaki

AU - Suenaga, Atsushi

AU - Taiji, Makoto

PY - 2012/11/6

Y1 - 2012/11/6

N2 - The process of binding of small ligands to dihydrofolate reductase protein has been investigated using all-atom molecular dynamics simulations. The existence of a mechanism that facilitates the search of the binding site by the ligand is demonstrated. The mechanism consists of ligand diffusing on the protein’s surface. It has been discussed in the literature before, but has not been explicitly confirmed for realistic molecular systems. The strength of this nonspecific binding is roughly estimated and found to be essential for the binding kinetics.

AB - The process of binding of small ligands to dihydrofolate reductase protein has been investigated using all-atom molecular dynamics simulations. The existence of a mechanism that facilitates the search of the binding site by the ligand is demonstrated. The mechanism consists of ligand diffusing on the protein’s surface. It has been discussed in the literature before, but has not been explicitly confirmed for realistic molecular systems. The strength of this nonspecific binding is roughly estimated and found to be essential for the binding kinetics.

KW - small ligand binding

KW - protein ligand binding

KW - binding rate

KW - facilitated binding

KW - surface diffusion

KW - mycobacterium tuberculosis dihydrofolate reductase

UR - http://www.scopus.com/inward/record.url?scp=84870843076&partnerID=8YFLogxK

UR - http://pubs.acs.org/doi/abs/10.1021/jz301635h

U2 - 10.1021/jz301635h

DO - 10.1021/jz301635h

M3 - Article

VL - 3

SP - 3476

EP - 3479

JO - Journal of Physical Chemistry Letters

JF - Journal of Physical Chemistry Letters

SN - 1948-7185

IS - 23

ER -