Protein flexibility and conformational ensembles from kino-geometric modeling and sampling to motion planning
Internally funded project
Start date : 01.06.2014
End date : 31.03.2019
Project details
Scientific Abstract
Proteins are dynamic macromolecules that perform their biological functions by exchanging between different conformational substates on a broad range of spatial and temporal scales. As the underlying energy landscapes that govern these conformational changes are very rough and often contain high energy barriers, efficient, yet atomically detailed simulations to understand and predict biophysically relevant motions remain challenging.
This project aims at providing functional insights into protein molecular mechanisms from simplified kinematic and geometric modeling. Guided by the covalent bond structure of the molecule, we construct kinematic multi-body systems with dihedral degrees of freedom and non-covalent interactions as constraints, which allows us to efficiently analyze conformational flexibility and deform the protein while maintaining secondary structure. Our analyses show convincing agreement with experimental data from various resources and more detailed Molecular Dynamics simulations, demonstrating the power of kino-geometric models for fast insights into protein flexibility and functional mechanisms, with broad implications for drug design and human health.
