Systematic exploration of multiple drug binding sites

Mónika Bálint, Norbert Jeszenoi, István Horváth, David Van Der Spoel, C. Hetényi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: 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. Results: 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.

Original languageEnglish
Article number65
JournalJournal of Cheminformatics
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 28 2017

Fingerprint

Binding sites
wrap
drugs
flexibility
Binding Sites
drug
Pharmaceutical Preparations
Ligands
Cell signaling
proteins
Proteins
ligands
tyrosine
Mitogens
Hydration
Antineoplastic Agents
Protein-Tyrosine Kinases
hydration
Molecular dynamics
Monolayers

Keywords

  • Complex
  • Dissociation
  • Flexibility
  • Interaction
  • Peptide
  • Pharmacodynamics
  • Pocket
  • Search
  • Structure
  • Water

ASJC Scopus subject areas

  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Computer Graphics and Computer-Aided Design
  • Library and Information Sciences

Cite this

Systematic exploration of multiple drug binding sites. / Bálint, Mónika; Jeszenoi, Norbert; Horváth, István; Van Der Spoel, David; Hetényi, C.

In: Journal of Cheminformatics, Vol. 9, No. 1, 65, 28.12.2017.

Research output: Contribution to journalArticle

Bálint, Mónika ; Jeszenoi, Norbert ; Horváth, István ; Van Der Spoel, David ; Hetényi, C. / Systematic exploration of multiple drug binding sites. In: Journal of Cheminformatics. 2017 ; Vol. 9, No. 1.
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