Structural Biology

 

Chazin
Walter ChazinMeiler
Jens Meiler

The Center for Structural Biology (CSB, csb.vanderbilt.edu), works with Vanderbilt collaborators through its computational outreach program, to bring a structural view to their research problems. This trans-institutional program has served dozens of Departments, Institutes, and Centers across campus. Projects often call for building homology models for proteins of unknown structure, performing energetic analysis of mutations, or structure-based drug design. We also use molecular dynamics calculations to simulate motions and conformational changes of protein systems, to gain insight into how these molecular machines function. Projects are conducted by Jonathan Sheehan, Ph.D. and Jarrod Smith, Ph.D. Professors Jens Meiler and Terry Lybrand act as consultants.The Meiler Laboratory (www.meilerlab.org)seeks to fuse computational and experimental efforts to investigate proteins, the fundamental molecules of biology, and their interactions with small molecule substrates, therapeutics, or probes. We develop computational methods with three major ambitions in mind.

  • To enable protein structure elucidation of membrane proteins the primary target of most therapeutics and large macromolecular complexes such as viruses;
  • Design proteins with novel structure and/or function to explore novel approaches to protein therapeutics and deepen our understanding of protein folding pathways.
  • Understand the relation between chemical structure and biological activity quantitatively in order to design more efficient and more specific drugs.

ACCRE enables us to split a single large problem that would otherwise take months to complete, across scores of computers running in parallel. ACCRE provides central processing units (CPUs) as well as graphics processing units (GPUs) tailored for our needs unlocking a significant research tool that was previously unavailable to our outreach collaborations. For example:

  • We test new protein folding algorithms during the Critical Assessment of protein Structure Prediction (CASP) experiment by predicting the structure of a protein 20 000 times in parallel on 500 CPUs.
  • We virtually screen libraries of up to 30 000 000 molecules for biological activity against target proteins of interest. The GPU cluster accelerates these calculations by a factor of 80-200.
  • We gear up to run molecular dynamics simulations with the software package AMBER on GPUs leveraging a recent methodological advancement for Vanderbilt researchers.
  • CPUs with high memory enable us to process large datasets such as cryo-Electron Microscopy density maps of the Adenovirus to determine the structure of its protein components.
Links:
Professor Walter Chazin’s page
Professor Jens Meiler’s page
Center for Structural Biology
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