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LIGAND DOCKING TO PROTEINS WITH DISCRETE SIDE-CHAIN FLEXIBILITY
被引:258
作者
:
LEACH, AR
论文数:
0
引用数:
0
h-index:
0
机构:
Department of Chemistry University of Southampton Southampton
LEACH, AR
机构
:
[1]
Department of Chemistry University of Southampton Southampton
来源
:
JOURNAL OF MOLECULAR BIOLOGY
|
1994年
/ 235卷
/ 01期
关键词
:
AUTOMATED MOLECULAR DOCKING;
CONFORMATIONAL SEARCH;
CONFORMATIONAL ENTROPY;
TREE SEARCH;
ROTAMER LIBRARY;
D O I
:
10.1016/S0022-2836(05)80038-5
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
:
An algorithm is described that explores the conformational degrees of freedom of the amino acid side-chains and of the ligand when docking a putative ligand into a receptor site. For a given orientation of the ligand relative to the protein, the method can find the lowest energy combination of amino acid side-chains and ligand conformations as well as all other combinations in order of increasing energy within a specified energy cutoff. The amino acid side-chains and the ligand are restricted to discrete low-energy conformations, determined for the former by analysing high-resolution protein structures and in the latter case from a conformational analysis. Coupled to an algorithm for exploring the six degrees of orientational freedom of the ligand with respect to the receptor, the method can be used to perform conformationally flexible ligand docking. A combination of two search methods is employed to explore the conformational degrees of freedom: Dead End Elimination and the A* algorithm. When no ligand is present the approach can be used to predict the lowest energy combinations of side-chain conformations for a given protein backbone structure. The approach is employed to illustrate how such a procedure can be used to estimate the conformational entropy change that accompanies the formation of an intermolecular complex between a protein and a ligand and to demonstrate that the protein's conformational entropy may in some cases increase on binding the ligand. This is due to a modification of the protein's energy hypersurface that makes more conformational states accessible. Our results highlight the need for appropriate methods to estimate the strength of binding. © 1994 Academic Press Limited.
引用
收藏
页码:345 / 356
页数:12
相关论文
共 34 条
[1]
[Anonymous], AMBER 4 0
[2]
PROTEIN DATA BANK - COMPUTER-BASED ARCHIVAL FILE FOR MACROMOLECULAR STRUCTURES
[J].
BERNSTEIN, FC
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
BERNSTEIN, FC
;
KOETZLE, TF
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
KOETZLE, TF
;
WILLIAMS, GJB
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
WILLIAMS, GJB
;
MEYER, EF
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
MEYER, EF
;
BRICE, MD
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
BRICE, MD
;
RODGERS, JR
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
RODGERS, JR
;
KENNARD, O
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
KENNARD, O
;
SHIMANOUCHI, T
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
SHIMANOUCHI, T
;
TASUMI, M
论文数:
0
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h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
TASUMI, M
.
JOURNAL OF MOLECULAR BIOLOGY,
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KNOWLEDGE-BASED PREDICTION OF PROTEIN STRUCTURES AND THE DESIGN OF NOVEL MOLECULES
[J].
BLUNDELL, TL
论文数:
0
引用数:
0
h-index:
0
机构:
Laboratory of Molecular Biology, Department of Crystallography, Birbeck College, University of London, London WC1E 7HX, United Kingdom
BLUNDELL, TL
;
SIBANDA, BL
论文数:
0
引用数:
0
h-index:
0
机构:
Laboratory of Molecular Biology, Department of Crystallography, Birbeck College, University of London, London WC1E 7HX, United Kingdom
SIBANDA, BL
;
STERNBERG, MJE
论文数:
0
引用数:
0
h-index:
0
机构:
Laboratory of Molecular Biology, Department of Crystallography, Birbeck College, University of London, London WC1E 7HX, United Kingdom
STERNBERG, MJE
;
THORNTON, JM
论文数:
0
引用数:
0
h-index:
0
机构:
Laboratory of Molecular Biology, Department of Crystallography, Birbeck College, University of London, London WC1E 7HX, United Kingdom
THORNTON, JM
.
NATURE,
1987,
326
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REFINED CRYSTAL-STRUCTURE OF BOVINE BETA-TRYPSIN AT 1.8 A RESOLUTION .2. CRYSTALLOGRAPHIC REFINEMENT, CALCIUM-BINDING SITE, BENZAMIDINE BINDING-SITE AND ACTIVE-SITE AT PH 7.0
[J].
BODE, W
论文数:
0
引用数:
0
h-index:
0
机构:
MAX PLANCK INST BIOCHEM,8033 MARTINSRIED,FED REP GER
BODE, W
;
SCHWAGER, P
论文数:
0
引用数:
0
h-index:
0
机构:
MAX PLANCK INST BIOCHEM,8033 MARTINSRIED,FED REP GER
SCHWAGER, P
.
JOURNAL OF MOLECULAR BIOLOGY,
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PREDICTION OF THE FOLDING OF SHORT POLYPEPTIDE SEGMENTS BY UNIFORM CONFORMATIONAL SAMPLING
[J].
BRUCCOLERI, RE
论文数:
0
引用数:
0
h-index:
0
机构:
HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,CAMBRIDGE,MA 02138
BRUCCOLERI, RE
;
KARPLUS, M
论文数:
0
引用数:
0
h-index:
0
机构:
HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,CAMBRIDGE,MA 02138
KARPLUS, M
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BIOPOLYMERS,
1987,
26
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[6]
CHAIN CLOSURE WITH BOND ANGLE VARIATIONS
[J].
BRUCCOLERI, RE
论文数:
0
引用数:
0
h-index:
0
机构:
HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138
HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138
BRUCCOLERI, RE
;
KARPLUS, M
论文数:
0
引用数:
0
h-index:
0
机构:
HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138
HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138
KARPLUS, M
.
MACROMOLECULES,
1985,
18
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-2773
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DOCKING FLEXIBLE LIGANDS TO MACROMOLECULAR RECEPTORS BY MOLECULAR SHAPE
[J].
DESJARLAIS, RL
论文数:
0
引用数:
0
h-index:
0
机构:
AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965
DESJARLAIS, RL
;
SHERIDAN, RP
论文数:
0
引用数:
0
h-index:
0
机构:
AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965
SHERIDAN, RP
;
DIXON, JS
论文数:
0
引用数:
0
h-index:
0
机构:
AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965
DIXON, JS
;
KUNTZ, ID
论文数:
0
引用数:
0
h-index:
0
机构:
AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965
KUNTZ, ID
;
VENKATARAGHAVAN, R
论文数:
0
引用数:
0
h-index:
0
机构:
AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965
VENKATARAGHAVAN, R
.
JOURNAL OF MEDICINAL CHEMISTRY,
1986,
29
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:2149
-2153
[8]
THE DEAD-END ELIMINATION THEOREM AND ITS USE IN PROTEIN SIDE-CHAIN POSITIONING
[J].
DESMET, J
论文数:
0
引用数:
0
h-index:
0
机构:
CORVAS INT NV,B-9000 GHENT,BELGIUM
DESMET, J
;
DEMAEYER, M
论文数:
0
引用数:
0
h-index:
0
机构:
CORVAS INT NV,B-9000 GHENT,BELGIUM
DEMAEYER, M
;
HAZES, B
论文数:
0
引用数:
0
h-index:
0
机构:
CORVAS INT NV,B-9000 GHENT,BELGIUM
HAZES, B
;
LASTERS, I
论文数:
0
引用数:
0
h-index:
0
机构:
CORVAS INT NV,B-9000 GHENT,BELGIUM
LASTERS, I
.
NATURE,
1992,
356
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[10]
THE MIDAS DISPLAY SYSTEM
[J].
FERRIN, TE
论文数:
0
引用数:
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h-index:
0
FERRIN, TE
;
HUANG, CC
论文数:
0
引用数:
0
h-index:
0
HUANG, CC
;
JARVIS, LE
论文数:
0
引用数:
0
h-index:
0
JARVIS, LE
;
LANGRIDGE, R
论文数:
0
引用数:
0
h-index:
0
LANGRIDGE, R
.
JOURNAL OF MOLECULAR GRAPHICS,
1988,
6
(01)
:13
-&
←
1
2
3
4
→
共 34 条
[1]
[Anonymous], AMBER 4 0
[2]
PROTEIN DATA BANK - COMPUTER-BASED ARCHIVAL FILE FOR MACROMOLECULAR STRUCTURES
[J].
BERNSTEIN, FC
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
BERNSTEIN, FC
;
KOETZLE, TF
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
KOETZLE, TF
;
WILLIAMS, GJB
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
WILLIAMS, GJB
;
MEYER, EF
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
MEYER, EF
;
BRICE, MD
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
BRICE, MD
;
RODGERS, JR
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
RODGERS, JR
;
KENNARD, O
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
KENNARD, O
;
SHIMANOUCHI, T
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
SHIMANOUCHI, T
;
TASUMI, M
论文数:
0
引用数:
0
h-index:
0
机构:
BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973
TASUMI, M
.
JOURNAL OF MOLECULAR BIOLOGY,
1977,
112
(03)
:535
-542
[3]
KNOWLEDGE-BASED PREDICTION OF PROTEIN STRUCTURES AND THE DESIGN OF NOVEL MOLECULES
[J].
BLUNDELL, TL
论文数:
0
引用数:
0
h-index:
0
机构:
Laboratory of Molecular Biology, Department of Crystallography, Birbeck College, University of London, London WC1E 7HX, United Kingdom
BLUNDELL, TL
;
SIBANDA, BL
论文数:
0
引用数:
0
h-index:
0
机构:
Laboratory of Molecular Biology, Department of Crystallography, Birbeck College, University of London, London WC1E 7HX, United Kingdom
SIBANDA, BL
;
STERNBERG, MJE
论文数:
0
引用数:
0
h-index:
0
机构:
Laboratory of Molecular Biology, Department of Crystallography, Birbeck College, University of London, London WC1E 7HX, United Kingdom
STERNBERG, MJE
;
THORNTON, JM
论文数:
0
引用数:
0
h-index:
0
机构:
Laboratory of Molecular Biology, Department of Crystallography, Birbeck College, University of London, London WC1E 7HX, United Kingdom
THORNTON, JM
.
NATURE,
1987,
326
(6111)
:347
-352
[4]
REFINED CRYSTAL-STRUCTURE OF BOVINE BETA-TRYPSIN AT 1.8 A RESOLUTION .2. CRYSTALLOGRAPHIC REFINEMENT, CALCIUM-BINDING SITE, BENZAMIDINE BINDING-SITE AND ACTIVE-SITE AT PH 7.0
[J].
BODE, W
论文数:
0
引用数:
0
h-index:
0
机构:
MAX PLANCK INST BIOCHEM,8033 MARTINSRIED,FED REP GER
BODE, W
;
SCHWAGER, P
论文数:
0
引用数:
0
h-index:
0
机构:
MAX PLANCK INST BIOCHEM,8033 MARTINSRIED,FED REP GER
SCHWAGER, P
.
JOURNAL OF MOLECULAR BIOLOGY,
1975,
98
(04)
:693
-717
[5]
PREDICTION OF THE FOLDING OF SHORT POLYPEPTIDE SEGMENTS BY UNIFORM CONFORMATIONAL SAMPLING
[J].
BRUCCOLERI, RE
论文数:
0
引用数:
0
h-index:
0
机构:
HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,CAMBRIDGE,MA 02138
BRUCCOLERI, RE
;
KARPLUS, M
论文数:
0
引用数:
0
h-index:
0
机构:
HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,CAMBRIDGE,MA 02138
KARPLUS, M
.
BIOPOLYMERS,
1987,
26
(01)
:137
-168
[6]
CHAIN CLOSURE WITH BOND ANGLE VARIATIONS
[J].
BRUCCOLERI, RE
论文数:
0
引用数:
0
h-index:
0
机构:
HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138
HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138
BRUCCOLERI, RE
;
KARPLUS, M
论文数:
0
引用数:
0
h-index:
0
机构:
HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138
HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138
KARPLUS, M
.
MACROMOLECULES,
1985,
18
(12)
:2767
-2773
[7]
DOCKING FLEXIBLE LIGANDS TO MACROMOLECULAR RECEPTORS BY MOLECULAR SHAPE
[J].
DESJARLAIS, RL
论文数:
0
引用数:
0
h-index:
0
机构:
AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965
DESJARLAIS, RL
;
SHERIDAN, RP
论文数:
0
引用数:
0
h-index:
0
机构:
AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965
SHERIDAN, RP
;
DIXON, JS
论文数:
0
引用数:
0
h-index:
0
机构:
AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965
DIXON, JS
;
KUNTZ, ID
论文数:
0
引用数:
0
h-index:
0
机构:
AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965
KUNTZ, ID
;
VENKATARAGHAVAN, R
论文数:
0
引用数:
0
h-index:
0
机构:
AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965
VENKATARAGHAVAN, R
.
JOURNAL OF MEDICINAL CHEMISTRY,
1986,
29
(11)
:2149
-2153
[8]
THE DEAD-END ELIMINATION THEOREM AND ITS USE IN PROTEIN SIDE-CHAIN POSITIONING
[J].
DESMET, J
论文数:
0
引用数:
0
h-index:
0
机构:
CORVAS INT NV,B-9000 GHENT,BELGIUM
DESMET, J
;
DEMAEYER, M
论文数:
0
引用数:
0
h-index:
0
机构:
CORVAS INT NV,B-9000 GHENT,BELGIUM
DEMAEYER, M
;
HAZES, B
论文数:
0
引用数:
0
h-index:
0
机构:
CORVAS INT NV,B-9000 GHENT,BELGIUM
HAZES, B
;
LASTERS, I
论文数:
0
引用数:
0
h-index:
0
机构:
CORVAS INT NV,B-9000 GHENT,BELGIUM
LASTERS, I
.
NATURE,
1992,
356
(6369)
:539
-542
[9]
DIXON JS, 1992, IN PRESS 9TH EUR S S
[10]
THE MIDAS DISPLAY SYSTEM
[J].
FERRIN, TE
论文数:
0
引用数:
0
h-index:
0
FERRIN, TE
;
HUANG, CC
论文数:
0
引用数:
0
h-index:
0
HUANG, CC
;
JARVIS, LE
论文数:
0
引用数:
0
h-index:
0
JARVIS, LE
;
LANGRIDGE, R
论文数:
0
引用数:
0
h-index:
0
LANGRIDGE, R
.
JOURNAL OF MOLECULAR GRAPHICS,
1988,
6
(01)
:13
-&
←
1
2
3
4
→