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13:57
Bio-layer Interferometry for Measuring Kinetics of Protein-protein Interactions and Allosteric Ligand Effects
Published on: February 18, 2014
Bioisosterism: quantitation of structure and property effects
1Center for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, VA 23284, USA. kier@mail2.vcu.edu
Chemistry & Biodiversity
|December 29, 2006
Summary
Bioisosterism aids drug design by analyzing molecular groups. This method uses electrotopological state, volume, and polarity for effective lead compound development.
Area of Science:
- Medicinal Chemistry
- Computational Chemistry
- Drug Discovery
Background:
- Bioisosterism is a key strategy in medicinal chemistry for optimizing drug properties.
- Selecting appropriate bioisosteres is crucial for successful lead compound development and molecular modification.
- Existing methods for bioisostere selection can be complex and require specialized expertise.
Purpose of the Study:
- To present a systematic method for selecting molecular groups based on bioisosterism principles.
- To introduce three key group-structure characteristics for evaluating bioisosteres.
- To provide practical tools for guiding bioisostere selection in drug design.
Main Methods:
- Utilizing the E-State value to quantify the electrotopological impact of attached atoms.
- Estimating molecular group volume using electron counts (sigma, pi, lone-pair n) via valence and connectivity delta values.
- Describing molecular polarity using the polarity index Q(v).
Main Results:
- Demonstration of the three group-structure characteristics (E-State, volume, polarity) with common molecular groups.
- Development of parameter spaces that visually encode these attributes for bioisostere evaluation.
- Validation of the method's utility in guiding selection during late-stage drug design.
Conclusions:
- The presented bioisosterism approach offers a practical framework for molecular modification in drug discovery.
- Quantitative assessment of electrotopological impact, volume, and polarity facilitates informed bioisostere selection.
- This method enhances decision-making processes in lead compound development and optimization.
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