DOI: 10.1002/prot.340230403. An automated method for dynamic ligand design

An automated method for dynamic ligand design

10.1002/prot.340230403

Crossref journal-article

Wiley

Proteins: Structure, Function, and Bioinformatics (311)

Abstract

AbstractAn automated method for the dynamic ligand design (DLD) for a binding site of known structure is described. The method can be used for the creation of de novo ligands and for the modification of existing ligands. The binding site is saturated with atoms (sp3 carbon atoms in the present implementation) that form molecules under the influence of a potential function that joins atoms to each other with the correct stereochemistry. The resulting molecules are linked to precomputed functional group minimum energy positions in the binding site. The generalized potential function allows atoms to sample a continuous parameter space that includes the Cartesian coordinates and their occupancy and type, e.g., the method allows change of an sp3 carbon into an sp2 carbon or oxygen. A parameter space formulated in this way can then be sampled and optimized by a variety of methods. In this work, molecules are generated by use of a Monte Carlo simulated annealing algorithm. The DLD method is illustrated by its application to the binding site of FK506 binding protein (FKBP), an immunophilin. De novo ligands are designed and modification of the immunosuppressant drug FK506 are suggested. The results demonstrate that the dynamic ligand design approach can automatically construct ligands which complement both the shape and charge distribution of the binding site. © 1995 Wiley‐Liss, Inc.

Bibliography

Miranker, A., & Karplus, M. (1995). An automated method for dynamic ligand design. Proteins: Structure, Function, and Bioinformatics, 23(4), 472â490. Portico.

Authors 2

Andrew Miranker (first)
Martin Karplus (additional)

References 31 Referenced 79

10.1002/prot.340110104
10.1021/jm00067a013
10.1002/prot.340190305
{'key': 'e_1_2_1_5_2', 'volume-title': 'Computer Simulations of Liquids', 'author': 'Allen M. P.', 'year': '1987'} / Computer Simulations of Liquids by Allen M. P. (1987)
{'key': 'e_1_2_1_6_2', 'volume-title': 'Numerical Recipes: The Art of Scientific Computing', 'author': 'Press W. H.', 'year': '1987'} / Numerical Recipes: The Art of Scientific Computing by Press W. H. (1987)
{'key': 'e_1_2_1_7_2', 'volume-title': 'Handbook of Genetic Algorithms', 'author': 'Davis L.', 'year': '1991'} / Handbook of Genetic Algorithms by Davis L. (1991)
10.1126/science.220.4598.671
10.1016/0022-2836(87)90041-6
10.1073/pnas.87.17.6644
10.1007/BF00125945
10.1007/BF00124349
10.1002/prot.340120105
10.1007/BF00124387
10.1007/BF00125322
10.1007/BF00119865
10.1002/prot.340110409
10.1007/BF00126441
10.1007/BF00126746
10.1002/jcc.540040211
10.1002/jcc.540080703
10.1016/0022-2836(91)80222-G
10.1107/S0021889883010985
10.1007/978-1-4613-1627-5
{'key': 'e_1_2_1_25_2', 'volume-title': 'Simulated annealing and Boltzmann machines: A stochastic approach to combinatorial optimization and neural computing', 'author': 'Aarts E.', 'year': '1989'} / Simulated annealing and Boltzmann machines: A stochastic approach to combinatorial optimization and neural computing by Aarts E. (1989)
10.1214/aoms/1177692644
10.1002/9780470141205
10.1002/prot.340200105
10.1126/science.1709302
10.1126/science.8211144
Stultz C. Karplus M.Computational combinatorial chemistry for de novo ligand design: review. (submitted).
Caflisch A. Karplus M.Perspectives in drug discovery and design. (in press).

Dates

Type	When
Created	20 years, 3 months ago (May 28, 2005, 9:48 p.m.)
Deposited	1 year, 10 months ago (Oct. 26, 2023, 7:43 p.m.)
Indexed	1 month ago (Aug. 2, 2025, 1:10 a.m.)
Issued	29 years, 9 months ago (Dec. 1, 1995)
Published	29 years, 9 months ago (Dec. 1, 1995)
Published Online	21 years, 6 months ago (Feb. 3, 2004)
Published Print	29 years, 9 months ago (Dec. 1, 1995)

Funders 0

None

BibTeX

@article{Miranker_1995, title={An automated method for dynamic ligand design}, volume={23}, ISSN={1097-0134}, url={http://dx.doi.org/10.1002/prot.340230403}, DOI={10.1002/prot.340230403}, number={4}, journal={Proteins: Structure, Function, and Bioinformatics}, publisher={Wiley}, author={Miranker, Andrew and Karplus, Martin}, year={1995}, month=dec, pages={472–490} }

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