Steered Molecular Dynamics for Investigating the Interactions Between Insulin Receptor Tyrosine Kinase (IRK) and Variants of Protein Tyrosine Phosphatase 1B (PTP1B)

被引：8

作者：

Nguyen, Hung ^{[1
]}

Do, Nhat ^{[2
]}

Phan, Tuyn ^{[1
]}

Pham, Tri ^{[1
]}

机构：

[1] Inst Computat Sci & Technol, Ho Chi Minh City, Vietnam

[2] Univ Med & Pharm, Dept Med Chem, Fac Pharm, Ho Chi Minh City, Vietnam

来源：

APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY | 2018年 / 184卷 / 02期

关键词：

SMD; IRK-PTP1Bs; MM-PBSA; Binding free energy; SUBSTRATE-TRAPPING MUTANT; CRYSTAL-STRUCTURE; HIGHLY EFFICIENT; SKELETAL-MUSCLE; FREE-ENERGIES; MODELS; RESISTANCE; SOLVENT; COMPLEX; OBESITY;

D O I：

10.1007/s12010-017-2549-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The aim of this study is to use steered molecular dynamics to investigate the dissociation process between IRK and PTP1Bs for wild type and five mutants (consisting of p.D181E, p.D181A, p.Q262A, p.D181A-Y46F, and p.D181A-Q262A). The gained results are observed not only the unbinding mechanism of IRK-PTP1B complexes came from pulling force profile, number of hydrogen bonds, and interaction energy between IRK and PTP1Bs but also described PTP1B's point mutations could variably change its binding affinity towards IRK. Additionally, the binding free energy calculated by Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) is also revealed that electrostatic energy and polar solvation energy mainly made up the binding free energy of PTP1B-IRK complexes.

引用

页码：401 / 413

页数：13

共 42 条

[1] INCREASED ABUNDANCE OF SPECIFIC SKELETAL-MUSCLE PROTEIN-TYROSINE PHOSPHATASES IN A GENETIC MODEL OF INSULIN-RESISTANT OBESITY AND DIABETES-MELLITUS [J].

AHMAD, F ;

GOLDSTEIN, BJ .

METABOLISM-CLINICAL AND EXPERIMENTAL, 1995, 44 (09) :1175-1184

[2] 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

[3] MOLECULAR-DYNAMICS WITH COUPLING TO AN EXTERNAL BATH [J].

BERENDSEN, HJC ;

POSTMA, JPM ;

VANGUNSTEREN, WF ;

DINOLA, A ;

HAAK, JR .

JOURNAL OF CHEMICAL PHYSICS, 1984, 81 (08) :3684-3690

[4] A New Highly Efficient Substrate-trapping Mutant of Protein Tyrosine Phosphatase 1B (PTP1B) Reveals Full Autoactivation of the Insulin Receptor Precursor [J].

Boubekeur, Samira ;

Boute, Nicolas ;

Pagesy, Patrick ;

Zilberfarb, Vladimir ;

Christeff, Nevena ;

Issad, Tarik .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (22) :19373-19380

[5] Protein-tyrosine phosphatase-1B acts as a negative regulator of insulin signal transduction [J].

Byon, JCH ;

Kusari, AB ;

Kusari, J .

MOLECULAR AND CELLULAR BIOCHEMISTRY, 1998, 182 (1-2) :101-108

[6] Elevated expression and activity of protein-tyrosine phosphatase 1B in skeletal muscle of insulin-resistant type II diabetic Goto-Kakizaki rats [J].

Dadke, SS ;

Li, HC ;

Kusari, AB ;

Begum, N ;

Kusari, J .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 274 (03) :583-589

[7] PARTICLE MESH EWALD - AN N.LOG(N) METHOD FOR EWALD SUMS IN LARGE SYSTEMS [J].

DARDEN, T ;

YORK, D ;

PEDERSEN, L .

JOURNAL OF CHEMICAL PHYSICS, 1993, 98 (12) :10089-10092

[8] Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene [J].

Elchebly, M ;

Payette, P ;

Michaliszyn, E ;

Cromlish, W ;

Collins, S ;

Loy, AL ;

Normandin, D ;

Cheng, A ;

Himms-Hagen, J ;

Chan, CC ;

Ramachandran, C ;

Gresser, MJ ;

Tremblay, ML ;

Kennedy, BP .

SCIENCE, 1999, 283 (5407) :1544-1548

[9] Development of ''substrate-trapping'' mutants to identify physiological substrates of protein tyrosine phosphatases [J].

Flint, AJ ;

Tiganis, T ;

Barford, D ;

Tonks, NK .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (05) :1680-1685

[10]

Hess B, 1997, J COMPUT CHEM, V18, P1463, DOI 10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO

← 1 2 3 4 5 →