Abstract

Knowingthestructure,dynamicsandligandbindingspecificityofproteinsandnucleicacidsisessentialto understandingthemechanismsofhumandiseaseandtotheoptimaldesignofmoleculesthatcanintervene therapeuticallyindiseaseprocesses.NuclearMagneticResonance(NMR)Spectroscopyisoneofthemost versatiletechniquesforobtainingthismolecularinformation.ThistremendousvalueofNMRinbiomedical scienceisonlyrealizedthroughtheapplicationofpowerfulcomputationaltools.Ourgoalinthisprojectisto extendandhardenthreeexistingsoftwareprogramsforthecomputationalanalysisofNMRdataintoa powerful,butuser-friendly,integratedsuite.HavingeffectivesoftwareforNMR,asweareproposing,is especiallycriticalaswerealizethatthedeepinsightintomacromolecularstructureandfunctioncomesnot fromasingletechniquelikeNMR,butfromthecomplementaryinformationfromvarioustechniquesincluding NMR,X-raycrystallography,andCryo-electronmicroscopy.Scientistsarenolongerseeingthesetechniques asspecializedtechniquesusablebyonlydomainexperts,butasacollectionoftechniquesthatcanandshould beappliedtogether.DespitethisessentialroleforNMRandthekeyneedforaccessiblecomputationaltoolsin itsuse,theredoesnotexistanintegratedsoftwareenvironmentthatspansthemajorstepsofmacromolecular NMRanalysis.Researchersmustuseavarietyoftoolsfromdifferentlabsthathavedifferentprogramming languages,scriptingtools,namingconventions,graphicalinterfaces,documentationstylesetc.Theproject proposedhereaimstoresolvethisimportantissuebythefurtherdevelopmentandhardeningofthreeexisting softwareapplications,allpreviouslydevelopedbythePI,intoanintegratedsoftwaresuite,NMRFx.NMRFx ProcessorwillprovidethesignalprocessingnecessarytotransformNMRdataintousablespectra.NMRFx ViewerwillprovideadvancedtoolsforvisualizingandanalyzingtheNMRspectra.NMRFxStructurewillallow calculatingmacromolecularstructuresconsistentwiththedata,andcalculatingstructuredependentNMR propertiessuchaschemicalshifts.Integratingthetoolswillnotonlymaketheirusemoreaccessibleand efficient,buttightintegrationwillallownewapproachestocomputationalanalysisthatmoveawayfromthe traditionallinearsequenceofstepsintoamoreholisticapproachtoextractinginformationfromthedata. Developmentoftheintegratedsoftwareplatformproposedherewillsubstantiallylowerthebarrierandbetter supportnewusersinaccessingtheimportantinformationthatNMRcanprovide.Weproposethatbyproviding new,andevenexperiencedusers,withasoftwaretoolsetthathasacommoninstallationprotocol,interface style,datastructures,andoveralldesign,wecansubstantiallylowerthesebarrierstouse.Doingthiswill maketheuseofNMRtechniquesmoreaccessibletoawiderpopulationofresearchersandincreasetheuse ofNMRinabroadrangeofbiologicalresearchareasthatimpactonhumanhealth.

Public Health Relevance

Knowingthestructure,dynamicsandligandbindingspecificityofproteinsandnucleicacidsisessentialto understandingthemechanismsofhumandiseaseandtotheoptimaldesignofmoleculesthatcanintervene therapeuticallyindiseaseprocesses.NuclearMagneticResonance(NMR)Spectroscopyisoneofthemost versatiletechniquesforobtainingthismolecularinformation.Thisresearchwillextendandhardenan integrated,softwaresuiteforprocessing,analyzing,andusingNMRdata,andtherebymaketheuseofthese techniquesfasterandmoreaccessibletoawiderpopulationofresearchers.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM123012-04
Application #
9977225
Study Section
Macromolecular Structure and Function D Study Section (MSFD)
Program Officer
Krepkiy, Dmitriy
Project Start
2017-09-15
Project End
2021-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

Name
Advanced Science Research Center
Department
Type
Organized Research Units
DUNS #
831361857
City
New York
State
NY
Country
United States
Zip Code
10031