Advances to tackle backbone flexibility in protein docking. (April 2021)

• Record Type: Journal Article
• Authors: Harmalkar, Ameya; Gray, Jeffrey J
• Is Part Of: Current opinion in structural biology. Volume 67(2021)
• Page Start: 178
• Page End: 186
• Publication Date: 2021-04
• Subjects: Molecular biology -- Periodicals; 570
• DOI: 10.1016/j.sbi.2020.11.011
• Languages: English
• ISSNs: 0959-440X

Abstract

Graphical abstract: Abstract : Computational docking methods can provide structural models of protein–protein complexes, but protein backbone flexibility upon association often thwarts accurate predictions. In recent blind challenges, medium or high accuracy models were submitted in less than 20% of the 'difficult' targets (with significant backbone change or uncertainty). Here, we describe recent developments in protein–protein docking and highlight advances that tackle backbone flexibility. In molecular dynamics and Monte Carlo approaches, enhanced sampling techniques have reduced time-scale limitations. Internal coordinate formulations can now capture realistic motions of monomers and complexes using harmonic dynamics. And machine learning approaches adaptively guide docking trajectories or generate novel binding site predictions from deep neural networks trained on protein interfaces. These tools poise the field to break through the longstanding challenge of correctly predicting complex structures with significant conformational change.