Development of likelihood-based methods in structural biology (360G-Wellcome-209407_Z_17_Z)

£1,916,285

<p>I propose to build on our development of new likelihood-based methods for structural biology, transposing approaches that have had great impact in macromolecular crystallography to the new area of cryo-EM.&nbsp; 1) In crystallography we will enable the solution of difficult structures (poor data or poor starting models) that still evade current methods.&nbsp; New statistical innovations will automate the clustering of alternative molecular replacement models into sensible ensembles representing different conformations. &nbsp;2) We will exploit a promising new approach to the determination of substructures for SAD phasing, based on our SAD likelihood function.&nbsp; 3) In cryo-EM we will investigate the propagation of errors in reconstructions, building on this understanding to devise improved likelihood-based methods to dock atomic models into cryo-EM maps, particularly those challenging cases determined at low resolution such as sub-tomogram averages.&nbsp; The implications of multi-variate cryo-EM likelihood targets will be explored, with potential applications in the angular deconvolution of cryo-EM maps.&nbsp; 4) Finally, we will develop a new approach to modelling macromolecular structures at low resolution, using interactive molecular dynamics flexible fitting to combine high-quality potential functions with likelihood targets.</p>

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Grant Details

Amount Awarded 1916285
Applicant Surname Read
Approval Committee Science Interview Panel
Award Date 2017-11-28T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Principal Research Fellowship Renewal
Internal ID 209407/Z/17/Z
Lead Applicant Prof Randy Read
Planned Dates: End Date 2023-06-01T00:00:00+00:00
Planned Dates: Start Date 2018-06-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Gillian Griffiths