Ensemble-based evaluation for protein structure models.
Comparing protein tertiary structures is a fundamental procedure in structural biology and protein bioinformatics. Structure comparison is important particularly for evaluating computational protein structure models. Most of the model structure evaluation methods perform rigid body superimposition of a structure model to its crystal structure and measure the difference of the corresponding residue or atom positions between them. However, these methods neglect intrinsic flexibility of proteins by treating the native structure as a rigid molecule. Because different parts of proteins have different levels of flexibility, for example, exposed loop regions are usually more flexible than the core region of a protein structure, disagreement of a model to the native needs to be evaluated differently depending on the flexibility of residues in a protein.



We propose a score named FlexScore for comparing protein structures that consider flexibility of each residue in the native state of proteins. Flexibility information may be extracted from experiments such as NMR or molecular dynamics simulation. FlexScore considers an ensemble of conformations of a protein described as a multivariate Gaussian distribution of atomic displacements and compares a query computational model with the ensemble. We compare FlexScore with other commonly used structure similarity scores over various examples. FlexScore agrees with experts' intuitive assessment of computational models and provides information of practical usefulness of models.



https://bitbucket.org/mjamroz/flexscore



dkihara@purdue.edu



Supplementary data are available at Bioinformatics online.
Department of Chemistry, University of Warsaw, Warsaw, 02-093, Poland.
Michal
M
Jamroz
Department of Chemistry, University of Warsaw, Warsaw, 02-093, Poland.
Andrzej
A
Kolinski
Department of Biological Sciences Department of Computer Science, Purdue University, West Lafayette, IN 47907, USA.
Daisuke
D
Kihara
D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins
D011506:Proteins