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Dynamics and Mechanisms

The project comprises of various sub-projects as follows :

1. Protein and RNA Dynamics

We often use elastic network models to obtain simple dynamics.  We have published packages to carry out these studies such as :

  • Multiple Protein Structures Map Out Intrinsically Favored Conformational Changes
  • New Elastic Network Models with Springs Based on Variability of Distances among Experimental Sets of Structures
  • Force Driven Conformational Transitions
  • Protein Dynamic Communities from Elastic Network Models Reproduce the Communities Defined by Molecular Dynamics
  • Unstable Mutants Cause Changes in the Protein Community Structure 

2. Biomolecular Mechanisms

Some of the systems we have studied are as follows :

  • Ribosome
  • Enzyme mechanism of triosephosphate isomerase (TIM)
  • Processing mechanisms - Reverse transcriptase
  • Single molecule pulling experiments
  • Computation of the time dependent dynamics of protein residues for elastic network models
  • The importance of slow motions for protein functional loops
  • Triose Phosphate Isomerase and Aldolase – steps on glycolysis pathway
  • FBA and TIM Architectures and Structural Similarity
  • ACP movement pathway within the Fatty Acid Synthesis Machine
  • Computing the transport pathways through membrane transport proteins
  • Cadherin dynamics for cell adhesion

3. Recent Extraction of Local Entropies from Structures
Previous entropies that were described in the proposal had been global in character. During this period we have evaluated the local entropies and shown how these are closely related to entropies computed from molecular dynamics, but can be computed directly from a single structure, in a much simpler way. This work focused on the atomic packing details, which are calculated by combining Voronoi diagrams and Delaunay tessellations. Even though the method is simple, the entropies computed exhibit an extremely high correlation with the entropies previously derived by other methods based on quasi-harmonic motions, quantum mechanics, and MD simulations. These packing-based entropies account directly for the local freedom and provide entropy for any individual protein structure that could be used to compute free energies directly during simulations for the generation of more reliable trajectories and also for better evaluations of modeled protein structures. Physico- chemical properties of amino acids are compared with these packing entropies to uncover the relationships with the entropies of different residue types. A public Packing Entropy webserver is provided at packing-, and the API is available within the PACKMAN ( package. This work provides a way to compute entropies for any protein structure, which could be incorporated into molecular dynamics or other sampling methods, and in this project directly into the free energy potentials. The publication has been accepted (P Khade, RL Jernigan, Entropies Derived from the Packing Geometries within a Single Protein Structure, ACS Omega, in press).

Funding Organizations: