Vagabond : bond-based parametrization reduces overfitting for refinement of proteins

DOI: 10.1107/S2059798321000826

Authors: Helen M. Ginn (Diamond Light Source)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section D Structural Biology , VOL 77

State: Published (Approved)
Published: April 2021

Abstract: Structural biology methods have delivered over 150 000 high-resolution structures of macromolecules, which have fundamentally altered our understanding of biology and our approach to developing new medicines. However, the description of molecular flexibility is instrinsically flawed and in almost all cases, regardless of the experimental method used for structure determination, there remains a strong overfitting bias during molecular model building and refinement. In the worst case this can lead to wholly incorrect structures and thus incorrect biological interpretations. Here, by reparametrizing the description of these complex structures in terms of bonds rather than atomic positions, and by modelling flexibility using a deterministic ensemble of structures, it is demonstrated that structures can be described using fewer parameters than in conventional refinement. The current implementation, applied to X-ray diffraction data, significantly reduces the extent of overfitting, allowing the experimental data to reveal more biological information in electron-density maps.

Journal Keywords: X-ray diffraction; refinement software; bonds; protein flexibility; models

Subject Areas: Information and Communication Technology, Technique Development, Biology and Bio-materials


Technical Areas:

Documents:
qj5007.pdf

Discipline Tags:

Information & Communication Technologies Computing & software technologies Life Sciences & Biotech Technique Development - Life Sciences & Biotech

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