Docking studies on PARP-1 inhibitors: insights into the role of a binding pocket water molecule

被引：56

作者：

Bellocchi, D ^{[1
]}

Macchiarulo, A ^{[1
]}

Costantino, G ^{[1
]}

Pellicciari, R ^{[1
]}

机构：

[1] Univ Perugia, Dipartimento Chim & Tecnol Farmaco, I-06123 Perugia, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2005年 / 13卷 / 04期

关键词：

PARP; docking; structural water; desolvation energy;

D O I：

10.1016/j.bmc.2004.11.024

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 binding mode of a series of competitive PARP-1 inhibitors was investigated employing a molecular docking approach by using Autodock 3.0. A particular attention was given to the role played by a water molecule present in some but not all the so far available crystal structures of the catalytic domain of PARP-1. Good correlation between calculated binding energies and experimental inhibitory activities was obtained either by including (r(2) = 0.87) or not (r(2) = 0.84) the structural water molecule. Closer inspection of our results suggested that this water molecule should be considered part of the hydration shell of polar inhibitors and not as a structural water. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：1151 / 1157

页数：7

共 28 条

[11] Design and synthesis of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. Part 4: Biological evaluation of imidazobenzodiazepines as potent PARP-1 inhibitors for treatment of ischemic injuries [J].

Ferraris, D ;

Ficco, RP ;

Dain, D ;

Ginski, M ;

Lautar, S ;

Lee-Wisdom, K ;

Liang, S ;

Lin, Q ;

Lu, MXC ;

Morgan, L ;

Thomas, B ;

Williams, LR ;

Zhang, J ;

Zhou, YN ;

Kalish, VJ .

BIOORGANIC & MEDICINAL CHEMISTRY, 2003, 11 (17) :3695-3707

[12] Resistance-modifying agents. 5. Synthesis and biological properties of quinazolinone inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) [J].

Griffin, RJ ;

Srinivasan, S ;

Bowman, K ;

Calvert, AH ;

Curtin, NJ ;

Newell, DR ;

Pemberton, LC ;

Golding, BT .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (26) :5247-5256

[13]

HAWKINS GD, AMSOL VERSION 6 8

[14]

Kinoshita T, 2004, FEBS LETT, V556, P43, DOI 10.5940/jcrsj.46.421

[15]

Morris GM, 1998, J COMPUT CHEM, V19, P1639, DOI 10.1002/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO

[16]

2-B

[17] Crystal structure of the catalytic fragment of murine poly(ADP-ribose) polymerase-2 [J].

Oliver, AW ;

Amé, JC ;

Roe, SM ;

Good, V ;

de Murcia, G ;

Pearl, LH .

NUCLEIC ACIDS RESEARCH, 2004, 32 (02) :456-464

[18]

Pellicciari R, 2004, PROGR MED CHEM, V42, P125, DOI 10.1016/S0079-6468(04)42003-7

[19] Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin-induced diabetes [J].

Pieper, AA ;

Brat, DJ ;

Krug, DK ;

Watkins, CC ;

Gupta, A ;

Blackshaw, S ;

Verma, A ;

Wang, ZQ ;

Snyder, SH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (06) :3059-3064

[20] Structure of the catalytic fragment of poly(ADP-ribose) polymerase from chicken [J].

Ruf, A ;

DeMurcia, JM ;

DeMurcia, GM ;

Schulz, GE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (15) :7481-7485

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