Protein flexibility and conformational ensembles from kino-geometric modeling, sampling and motion planning.

Internally funded project


Project Details

Project leader:
Prof. Dr.-Ing. Sigrid Leyendecker

Project members:
Dominik Budday

Contributing FAU Organisations:
Chair of Applied Dynamics

Start date: 01/06/2014


Research Fields

biomechanics
Chair of Applied Dynamics
multibody dynamics and robotics
Chair of Applied Dynamics


Abstract (technical / expert description):

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.


Publications

Fonseca, R., Budday, D., & van den Bedem, H. (2018). Collision-free poisson motion planning in ultra high-dimensional molecular conformation spaces. Journal of Computational Chemistry. https://dx.doi.org/10.1002/jcc.25138
Héliou, A., Budday, D., Fonseca, R., & van den Bedem, H. (2017). Fast, clash-free RNA conformational morphing using molecular junctions. Bioinformatics. https://dx.doi.org/10.1093/bioinformatics/btx127
Budday, D., Fonseca, R., Leyendecker, S., & van den Bedem, H. (2017). Frustration-guided motion planning reveals conformational transitions in proteins. Proteins-Structure Function and Bioinformatics, 85(10), 1795-1807. https://dx.doi.org/10.1002/prot.25333
Budday, D., Leyendecker, S., & van den Bedem, H. (2015). Geometric analysis characterizes molecular rigidity in generic and non-generic protein configurations. Journal of the Mechanics and Physics of Solids, 83, 36-47. https://dx.doi.org/10.1016/j.jmps.2015.06.006

Last updated on 2019-08-01 at 16:40