Bayesian-Maximum-Entropy Reweighting of IDP Ensembles Based on NMR Chemical Shifts

Abstract

Bayesian and Maximum Entropy approaches allow for a statistically sound and systematic fitting of experimental and computational data. Unfortunately, assessing the relative confidence in these two types of data remains difficult as several steps add unknown error. Here we propose the use of a validation-set method to determine the balance, and thus the amount of fitting. We apply the method to synthetic NMR chemical shift data of an intrinsically disordered protein. We show that the method gives consistent results even when other methods to assess the amount of fitting cannot be applied. Finally, we also describe how the errors in the chemical shift predictor can lead to an incorrect fitting and how using secondary chemical shifts could alleviate this problem.

Keywords

• Bayesian methods
• maximum entropy
• chemical shifts
• intrinsically disordered proteins
• protein ensembles
• structural modelling
• NMR
• molecular dynamics