Diffusional Channeling in the Sulfate-Activating Complex: Combined Continuum Modeling and Coarse-Grained Brownian Dynamics Studies

被引：21

作者：

Cheng, Yuhui ^{[1
,2
,3
]}

Chang, Chia-en A. ^{[6
]}

Yu, Zeyun ^{[4
]}

Zhang, Yongjie ^{[7
]}

Sun, Meihao ^{[8
]}

Leyh, Thomas S. ^{[8
]}

Holst, Michael J. ^{[4
]}

McCammon, J. Andrew ^{[1
,2
,3
,5
]}

机构：

[1] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Dept Math, La Jolla, CA 92093 USA

[5] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[6] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA

[7] Carnegie Mellon Univ, Dept Mech Engn, Pittsburgh, PA 15213 USA

[8] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10467 USA

来源：

BIOPHYSICAL JOURNAL | 2008年 / 95卷 / 10期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

D O I：

10.1529/biophysj.108.140038

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

Enzymes required for sulfur metabolism have been suggested to gain efficiency by restricted diffusion (i.e., channeling) of an intermediate APS(2)-between active sites. This article describes modeling of the whole channeling process by numerical solution of the Smoluchowski diffusion equation, as well as by coarse-grained Brownian dynamics. The results suggest that electrostatics plays an essential role in the APS(2)-channeling. Furthermore, with coarse-grained Brownian dynamics, the substrate channeling process has been studied with reactions in multiple active sites. Our simulations provide a bridge for numerical modeling with Brownian dynamics to simulate the complicated reaction and diffusion and raise important questions relating to the electrostatically mediated substrate channeling in vitro, in situ, and in vivo.

引用

页码：4659 / 4667

页数：9

共 46 条

[1] Molecular dynamics simulations of substrate channeling through an α-β barrel protein [J].

Amaro, R ;

Luthey-Schulten, Z .

CHEMICAL PHYSICS, 2004, 307 (2-3) :147-155

[2] Two crystal structures of dihydrofolate reductase-thymidylate synthase from Cryptosporidium hominis reveal protein-ligand interactions including a structural basis for observed antifolate resistance [J].

Anderson, AC .

ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, 2005, 61 :258-262

[3] REGULATION OF ENZYME FUNCTION [J].

ATKINSON, DE .

ANNUAL REVIEW OF MICROBIOLOGY, 1969, 23 :47-+

[4]

Baker N, 2000, J COMPUT CHEM, V21, P1343, DOI 10.1002/1096-987X(20001130)21:15<1343::AID-JCC2>3.0.CO

[5]

2-K

[6] Electrostatics of nanosystems: Application to microtubules and the ribosome [J].

Baker, NA ;

Sept, D ;

Joseph, S ;

Holst, MJ ;

McCammon, JA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (18) :10037-10041

[7] Gated binding of ligands to HIV-1 protease: Brownian dynamics simulations in a coarse-grained model [J].

Chang, Chia-En ;

Shen, Tongye ;

Trylska, Joanna ;

Tozzini, Valentina ;

McCammon, J. Andrew .

BIOPHYSICAL JOURNAL, 2006, 90 (11) :3880-3885

[8] Finite element analysis of the time-dependent Smoluchowski equation for acetylcholinesterase reaction rate calculations [J].

Cheng, Yuhui ;

Suen, Jason K. ;

Zhang, Deqiang ;

Bond, Stephen D. ;

Zhang, Yongjie ;

Song, Yuhua ;

Baker, Nathan A. ;

Bajaj, Chandrajit L. ;

Holst, Michael J. ;

McCammon, J. Andrew .

BIOPHYSICAL JOURNAL, 2007, 92 (10) :3397-3406

[9] Continuum simulations of acetylcholine diffusion with reaction-determined boundaries in neuromuscular junction models [J].

Cheng, Yuhui ;

Suen, Jason K. ;

Radic, Zoran ;

Bond, Stephen D. ;

Holst, Michael J. ;

McCammon, J. Andrew .

BIOPHYSICAL CHEMISTRY, 2007, 127 (03) :129-139

[10] ALTERNATIVE VIEW OF ENZYME-REACTIONS [J].

DEWAR, MJS ;

STORCH, DM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (08) :2225-2229

← 1 2 3 4 5 →