Title |
Systematic exploration of multiple drug binding sites
|
---|---|
Published in |
Journal of Cheminformatics, December 2017
|
DOI | 10.1186/s13321-017-0255-6 |
Pubmed ID | |
Authors |
Mónika Bálint, Norbert Jeszenői, István Horváth, David van der Spoel, Csaba Hetényi |
Abstract |
Targets with multiple (prerequisite or allosteric) binding sites have an increasing importance in drug design. Experimental determination of atomic resolution structures of ligands weakly bound to multiple binding sites is often challenging. Blind docking has been widely used for fast mapping of the entire target surface for multiple binding sites. Reliability of blind docking is limited by approximations of hydration models, simplified handling of molecular flexibility, and imperfect search algorithms. To overcome such limitations, the present study introduces Wrap 'n' Shake (WnS), an atomic resolution method that systematically "wraps" the entire target into a monolayer of ligand molecules. Functional binding sites are extracted by a rapid molecular dynamics shaker. WnS is tested on biologically important systems such as mitogen-activated protein, tyrosine-protein kinases, key players of cellular signaling, and farnesyl pyrophosphate synthase, a target of antitumor agents. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Turkey | 1 | 14% |
France | 1 | 14% |
Sweden | 1 | 14% |
Unknown | 4 | 57% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 3 | 43% |
Scientists | 3 | 43% |
Science communicators (journalists, bloggers, editors) | 1 | 14% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 39 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 7 | 18% |
Student > Master | 7 | 18% |
Researcher | 7 | 18% |
Student > Doctoral Student | 3 | 8% |
Student > Ph. D. Student | 3 | 8% |
Other | 6 | 15% |
Unknown | 6 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Chemistry | 11 | 28% |
Biochemistry, Genetics and Molecular Biology | 8 | 21% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 10% |
Agricultural and Biological Sciences | 3 | 8% |
Arts and Humanities | 1 | 3% |
Other | 5 | 13% |
Unknown | 7 | 18% |