Probing the Structure/Function/Dynamics Relationship in Biomolecular Complexes With Multiscale Computational Techniques

Information

  • Research Project
  • 10018044
  • ApplicationId
    10018044
  • Core Project Number
    R35GM119647
  • Full Project Number
    5R35GM119647-05
  • Serial Number
    119647
  • FOA Number
    RFA-GM-16-003
  • Sub Project Id
  • Project Start Date
    9/1/2016 - 8 years ago
  • Project End Date
    8/31/2021 - 3 years ago
  • Program Officer Name
    LYSTER, PETER
  • Budget Start Date
    9/1/2020 - 4 years ago
  • Budget End Date
    8/31/2021 - 3 years ago
  • Fiscal Year
    2020
  • Support Year
    05
  • Suffix
  • Award Notice Date
    9/9/2020 - 4 years ago

Probing the Structure/Function/Dynamics Relationship in Biomolecular Complexes With Multiscale Computational Techniques

Project Summary:    Over  the  last  two  decades,  enabled  by  progress  in  synchrotron  radiation  techniques,  molecular  biology  methods, and computational resources, there has been tremendous progress in determining the structure  of biomolecules that has led, in many cases, to deep structural insights.  But there is a third dimension to  biological  function,  namely  dynamics,  which  is,  as  yet,  underexplored.    This  has  created  a  serious  blind  spot  that  inhibits  progress  towards  a  full  understanding  of  macromolecular  functions  and  biological  processes.    The  broad  objective  of  this  proposal  is  to  develop  and  utilize  computer  simulations  that  address this deficiency in knowledge by rigorously modeling biomolecular dynamics in order to increase  our understanding of biological processes.  More specifically, we will pursue three interrelated projects.   First,  we  will  determine  how  chromatin  remodeling  factors  influence  the  dynamics  of  nucleosomes  and  chromatin fibers as a means of regulating gene expression.  Second, we will examine the mechanisms of  recognition and regulation by sortase enzymes, which are key virulence factors in Gram-­?positive bacteria.   Finally, we will develop computational methods that more effectively model the results of solution small  angle  X-­?ray  scattering  (SAXS)  experiments  for  diverse  biomolecular  complexes.    Completion  of  these  studies will reveal intricate details about the relationship between the structure, function, and dynamics  of multicomponent biomolecular complexes across a vast range of time and length scales.  Furthermore,  the synergy between the scientific goals, as well as the computational methods and strong experimental  collaborations in each of these projects, will foster new opportunities and areas of scientific inquiry that  the MIRA award will allow us to pursue.  Overall, this work will address a series of fundamental gaps in  knowledge  for  critical  biological  processes,  and  will  lay  the  foundation  for  future  studies  that  will  improve the treatment and prevention of human ailments.

IC Name
NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
  • Activity
    R35
  • Administering IC
    GM
  • Application Type
    5
  • Direct Cost Amount
    250000
  • Indirect Cost Amount
    107448
  • Total Cost
    357448
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    859
  • Ed Inst. Type
    SCHOOLS OF ARTS AND SCIENCES
  • Funding ICs
    NIGMS:357448\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    ILLINOIS INSTITUTE OF TECHNOLOGY
  • Organization Department
    PHYSICS
  • Organization DUNS
    042084434
  • Organization City
    CHICAGO
  • Organization State
    IL
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    606163717
  • Organization District
    UNITED STATES