Eurecon: Equidistant uniform rigid-body ensemble constructor.

Area of Science:

• Bioinformatics
• Computational Chemistry
• Structural Biology

Background:

• Conformational ensembles are crucial in bioinformatics for applications like molecular docking and virtual screening.
• Generating large numbers of near-native conformations efficiently is computationally challenging.
• Existing methods lack guarantees for achieving a specific root mean square deviation (RMSD) between generated and reference structures.

Purpose of the Study:

• To develop a fast algorithm for constructing rigid-body conformational ensembles with a fixed RMSD.
• To ensure generated conformations are uniformly distributed around the reference structure.
• To provide a computationally efficient tool for high-throughput applications in structural bioinformatics.

Main Methods:

• Developed a novel algorithm, Eurecon (Equidistant Uniform Rigid-body Ensemble CONstructor), implemented in C++.
• Algorithm achieves O(N + M) complexity for generating rigid-body transforms, where N is the number of atoms and M is the ensemble size.
• Eurecon avoids standard RMSD computations, enhancing efficiency.

Main Results:

• Eurecon successfully generates conformational ensembles with a guaranteed fixed RMSD.
• The generated conformations exhibit uniform distribution over the sphere of rigid-body motions.
• Demonstrated applicability on diverse systems: ligand-binding site, protein dimer in a membrane, and ribosomal complex.

Conclusions:

• Eurecon provides an efficient and accurate method for constructing rigid-body conformational ensembles.
• The algorithm's fixed RMSD property and uniform distribution are key advantages for near-native ensemble generation.
• Eurecon is a versatile tool applicable to various molecular systems and is available as a SAMSON Element.