Hierarchical and multi-resolution representation of protein flexibility

Abstract

In this article, we present a computational data structure called the Flexibility Tree (FT) that enables a multi-resolution and hierarchical encoding of molecular flexibility. This tree-like data structure allows the encoding of relatively small, yet complex sub-spaces of a protein's conformational space. These conformational sub-spaces are parameterized by a small number of variables and can be searched efficiently using standard global search techniques. The FT structure makes it straightforward to combine and nest a wide variety of motion types such as hinge, shear, twist, screw, rotameric side chains, normal modes and essential dynamics. Moreover, the ability to assign shapes to the nodes in a FT allows the interactive manipulation of flexible protein shapes and the interactive visualization of the impact of conformational changes on the protein's overall shape. We describe the design of the FT and illustrate the construction of such trees to hierarchically combine motion information obtained from a variety of sources ranging from experiment to user intuition, and describing conformational changes at different biological scales. We show that the combination of various types of motion helps refine the encoded conformational sub-spaces to include experimentally determined structures, and we demonstrate searching these sub-spaces for specific conformations.

p38α MAP Kinase C-Terminal Domain Binding Pocket Characterized by Crystallographic and Computational Analyses

“…Therefore, before conducting docking studies, we analyzed the optimal configuration of this cap and the hydrophobic pocket that it creates, through rotation of the cap using FlexTree 31. The cap was rotated in 1 degree increments +/−15° as a rigid structure, about the Pro242 and Thr263 pivot points (Fig.…”

Optimization Algorithms for Flexible Protein-Protein Docking

“…Zhao et al [3] recently presented Flexibility Tree (FT). The FT is a hierarchical data structure which represents conformational subspaces of proteins and full flexibility of small ligands.…”

Protein Flexibility in Structure‐Based Virtual Screening: From Models to Algorithms

“…An interesting data structure, called flexibility tree, can be employed in the search for the docked complex structure and it allows to combine several flexibility techniques [95]. The data structure hierarchically encodes the flexibility of a protein in variables that allow several protein parts to experience different kinds of moves.…”