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

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 struc

SUBMITTER: Ginn HM 

PROVIDER: S-EPMC8025884 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature