Flexibases: A way to enhance the use of molecular docking methods

@article{Kearsley1994FlexibasesAW,
  title={Flexibases: A way to enhance the use of molecular docking methods},
  author={Simon K. Kearsley and Dennis J. Underwood and Robert P. Sheridan and Michael D. Miller},
  journal={Journal of Computer-Aided Molecular Design},
  year={1994},
  volume={8},
  pages={565-582}
}
SummarySpecially expanded databases containing three-dimensional structures are created to enhance the utility of docking methods to find new leads, i.e., active compounds of pharmacological interest. The expansion is based on the automatic generation of a set of maximally dissimilar conformations. The ligand receptor system of methotrexate and dihydrofolate reductase is used to demonstrate the feasibility of creating flexibases and their utility in docking studies. 
Docking small-molecule ligands into active sites.
TLDR
The principal advances of the past year have been the development of new algorithmic approaches, several of which incorporate conformational flexibility, and the increased use of docking to identify leads in drug-discovery programmes. Expand
Docking and scoring in virtual screening for drug discovery: methods and applications
TLDR
Key concepts and specific features of small-molecule–protein docking methods are reviewed, selected applications are highlighted and recent advances that aim to address the acknowledged limitations of established approaches are discussed. Expand
Dock around the Clock – Current Status of Small Molecule Docking and Scoring
TLDR
This review addresses key issues of docking and scoring, a popular technique in structure-based drug design, and the pros and cons of computational tools currently used will be outlined as well as the integration of these methods in the lead finding and lead optimization process. Expand
Pharmacophore‐based molecular docking to account for ligand flexibility
TLDR
This work has shown that ligand flexibility can be included without prohibitively increasing the search time by docking ensembles of precomputed conformers from a conformationally expanded database by using a pharmacophore‐based docking method. Expand
Ligand-protein docking and rational drug design.
  • T. Lybrand
  • Computer Science, Medicine
  • Current opinion in structural biology
  • 1995
Over the past year there have been some interesting and significant advances in computer-based ligand-protein docking techniques and related rational drug-design tools, including flexible ligandExpand
Analysis and optimization of structure-based virtual screening protocols (1): exploration of ligand conformational sampling techniques.
  • A. Good, D. Cheney
  • Chemistry, Medicine
  • Journal of molecular graphics & modelling
  • 2003
TLDR
A number of software programs currently being used in conformer generation are studied, analyzing their ability to regenerate known ligand binding conformations, from the perspective of VS in general and SVS in particular. Expand
Computational methods for biomolecular docking.
TLDR
Methods for computer-aided molecular docking have to include a reasonably accurate model of energy and must be able to deal with the combinatorial complexity incurred by the molecular flexibility of the docking partners. Expand
Molecular recognition and docking algorithms.
  • N. Brooijmans, I. Kuntz
  • Computer Science, Medicine
  • Annual review of biophysics and biomolecular structure
  • 2003
TLDR
This review focuses on methodological developments relevant to the field of molecular docking, and summarizes several critical methodological issues that must be addressed in future developments. Expand
FlexAID: Revisiting Docking on Non-Native-Complex Structures
TLDR
FlexAID is introduced, a small-molecule docking algorithm that accounts for target side-chain flexibility and utilizes a soft scoring function, i.e. one that is not highly dependent on specific geometric criteria, based on surface complementarity, and demonstrates that FlexAID, unlike other programs, is robust against increasing structural variability. Expand
FlexAID: Revisiting docking on non native-complex structures
TLDR
FlexAID is introduced, a small-molecule docking algorithm that accounts for target side-chain flexibility and utilizes a soft scoring function, i.e. one that is not highly dependent on specific geometric criteria, based on surface complementarity, in order to predict the structure of ligand protein complexes at the atomic level. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 30 REFERENCES
Automated docking with grid‐based energy evaluation
The ability to generate feasible binding orientations of a small molecule within a site of known structure is important for ligand design. We present a method that combines a rapid, geometric dockingExpand
CLIX: A search algorithm for finding novel ligands capable of binding proteins of known three‐dimensional structure
TLDR
The CLIX algorithm is shown to be capable of predicting the correct binding geometry of sialic acid to a mutant influenzavirus hemagglutinin and of proposing a number of potential new ligands to this protein. Expand
Structure-Based Strategies for Drug Design and Discovery
TLDR
The combination of molecular structure determination and computation is emerging as an important tool for drug development and will be applied to acquired immunodeficiency syndrome (AIDS) and bacterial drug resistance. Expand
Using shape complementarity as an initial screen in designing ligands for a receptor binding site of known three-dimensional structure.
TLDR
A method for finding a wide assortment of chemical structures that are complementary to the shape of a macromoleculer receptor site whose X-ray crystallographic structure is known and described to the binding sites of papain and carbonic anhydrase. Expand
Automated docking of substrates to proteins by simulated annealing
The Metropolis technique of conformation searching is combined with rapid energy evaluation using molecular affinity potentials to give an efficient procedure for docking substrates to macromoleculesExpand
GenStar: A method for de novo drug design
TLDR
Tests of the method using HIV protease, FK506 binding protein and human carbonic anhydrase demonstrated that structures similar to known potent inhibitors may be generated with GenStar. Expand
A geometric approach to macromolecule-ligand interactions.
TLDR
A method to explore geometrically feasible alignments of ligands and receptors of known structure and finds distinctly different geometries that provide good steric fits seems well-suited for generating starting conformations for energy refinement programs and interactive computer graphics routines. Expand
Application of crystallographic and modeling methods in the design of purine nucleoside phosphorylase inhibitors.
  • S. Ealick, Y. Babu, +4 authors J. Secrist
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1991
TLDR
Among the compounds designed and synthesized are the most potent competitive inhibitors of purine nucleoside phosphorylase thus far reported. Expand
Docking flexible ligands to macromolecular receptors by molecular shape.
TLDR
A method to explore the interaction of flexible ligands with receptors of known geometry on the basis of molecular shape is presented and finds binding geometries for the ligand near that observed crystallographically as well as others that provide good steric fit with the receptor. Expand
Automated site-directed drug design using molecular lattices
TLDR
A new modeling program, BUILDER, that combines database searching techniques and structure generation algorithms within an interactive graphics modeling environment (MidasPlus) and its ability to produce novel structures is described. Expand
...
1
2
3
...