Defining a Global Map of Functional Group Based 3D Ligand-binding Motifs

Abstract

Uncovering conserved 3D protein-ligand binding patterns at the basis of functional groups (FGs) shared by a variety of small molecules can greatly expand our knowledge of protein-ligand interactions. Despite that conserved binding patterns for a few commonly used FGs have been reported in the literature, large-scale identification and evaluation of FG-based 3D binding motifs are still lacking. Here, we developed AFTME, an alignment-free method for automatic mapping of 3D motifs to different FGs of a specific ligand through two-dimensional clustering. Applying our method to 233 nature-existing ligands, we defined 481 FG-binding motifs that are highly conserved across different ligand-binding pockets. Systematic analysis further reveals four main classes of binding motifs corresponding to distinct sets of FGs. Combinations of FG-binding motifs facilitate proteins to bind a wide spectrum of ligands with various binding affinities. Finally, we showed that these general binding patterns are also applicable to target-drug interactions, providing new insights into structure-based drug design.

Research on new combined operating mechanism of HVCB

“…The test mechanical platform of the motor operating mechanism with variable stroke and load reaction is designed based on the angle variation range and load torque characteristics of the driving motor with different high-voltage switches in the process of opening and closing. The motion part of the mechanical platform is selected, and the motion and dynamics model of the variable load is established by using virtual prototyping technology [6][7] .The motion characteristics of the mechanical platform, the structure of the components in the system, the law of motion change, and the constraint relationship between the components are simulated, and the load torque characteristics of the mechanical platform in the rotation process are determined.…”