SMBp Group Meeting: Jeff Lotthammer (Holehouse)

Tuesday Jun 6, 2023, 2:00 PM → 3:00 PM America/New_York

3rd Floor Classroom/3-Flatiron Institute (162 5th Avenue)

Speaker: Jeff Lotthammer  (Holehouse)

 

Topic: Direct Prediction of Intrinsically Disordered Protein Conformational Properties From Sequence

 

Abstract: Intrinsically disordered regions (IDRs) are ubiquitous across all domains of life and play a range of functional roles. While folded domains are generally well-described by a single 3D structure, IDRs exist in a collection of interconverting states known as an ensemble. This structural heterogeneity means IDRs are largely absent from the PDB, contributing to a lack of computational approaches to predict ensemble conformational properties from sequence. Here we combine rational sequence design, large-scale molecular simulations, and deep learning to develop ALBATROSS, a deep learning model for predicting IDR ensemble dimensions from sequence. ALBATROSS enables the instantaneous prediction of ensemble average properties at proteome-wide scale. ALBATROSS is lightweight, easy-to-use, and accessible as both a locally installable software package and a point-and-click style interface in the cloud. We first demonstrate the applicability of our predictors by examining the generalizability of sequence-ensemble relationships in IDRs. Then, we leverage the high-throughput nature of ALBATROSS to characterize emergent biophysical behavior of IDRs within and between proteomes

Zoom Link: Join from PC, Mac, Linux, iOS or Android: https://simonsfoundation.zoom.us/j/91293230672?pwd=V1B6Wk9hVDdKWW9vSlRsczAwSHdHUT09

Passcode: 077023