Energy landscapes and drug design
Abstract
Recent developments in understanding the complexity and simplicity of biomolecular interactions and molecular recognition are discussed by exploiting the emerging universalities between protein folding and molecular recognition. Structure, thermodynamics and kinetics of ligand-protein binding are investigated for a diverse repertoire of inhibitor-protein complexes using the statistical theory of the energy landscapes. Simulated tempering dynamics studies with the simplified energy functions and all-atom molecular mechanics force fields combined with the weighted histogram analysis methods have provided further understanding into structural and energetic aspects of molecular recognition. The robust topology of the native structure appears to be a decisive factor contributing to the thermodynamics and dynamics of ligand-protein complexes. We also analyze the relevance of the energy landscape theory and the role of topology and structure in understanding molecular recognition mechanisms and evolutionary principles behind convergent solutions to stable intermolecular interfaces.
- Publication:
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APS March Meeting Abstracts
- Pub Date:
- March 2002
- Bibcode:
- 2002APS..MAR.U7004V