Improved estimates of coordinate error for molecular replacement.

Robert D Oeffner,Gábor Bunkóczi,Airlie J Mccoy,Randy J Read

doi:10.1107/s0907444913023512

Robert D Oeffner, Gábor Bunkóczi + Show 2 more

Open Access

https://doi.org/10.1107/s0907444913023512

Copy DOI

Abstract

The estimate of the root-mean-square deviation (r.m.s.d.) in coordinates between the model and the target is an essential parameter for calibrating likelihood functions for molecular replacement (MR). Good estimates of the r.m.s.d. lead to good estimates of the variance term in the likelihood functions, which increases signal to noise and hence success rates in the MR search. Phaser has hitherto used an estimate of the r.m.s.d. that only depends on the sequence identity between the model and target and which was not optimized for the MR likelihood functions. Variance-refinement functionality was added to Phaser to enable determination of the effective r.m.s.d. that optimized the log-likelihood gain (LLG) for a correct MR solution. Variance refinement was subsequently performed on a database of over 21,000 MR problems that sampled a range of sequence identities, protein sizes and protein fold classes. Success was monitored using the translation-function Z-score (TFZ), where a TFZ of 8 or over for the top peak was found to be a reliable indicator that MR had succeeded for these cases with one molecule in the asymmetric unit. Good estimates of the r.m.s.d. are correlated with the sequence identity and the protein size. A new estimate of the r.m.s.d. that uses these two parameters in a function optimized to fit the mean of the refined variance is implemented in Phaser and improves MR outcomes. Perturbing the initial estimate of the r.m.s.d. from the mean of the distribution in steps of standard deviations of the distribution further increases MR success rates.

Highlights

Molecular replacement (MR; Rossmann & Blow, 1962) relies on the evolutionary principle that two proteins with a high sequence identity are very likely to have similar secondary and tertiary structures and low root-mean-square deviation (r.m.s.d.) in coordinate positions
The translation-function Z-score (TFZ) for the top peak in the search was found to be a reliable indicator of successful MR, at least for this class of cases in which there is one molecule in the asymmetric unit
We investigated the dependence of the VRMS on the (VRMS/estimated VRMS (eVRMS)) was used to calibrate the perturbation of the SCOP class

Summary

Introduction

Molecular replacement (MR; Rossmann & Blow, 1962) relies on the evolutionary principle that two proteins with a high sequence identity are very likely to have similar secondary and tertiary structures and low root-mean-square deviation (r.m.s.d.) in coordinate positions. An estimate of the r.m.s.d. is an essential parameter used to calibrate likelihood functions in the maximum-likelihood approach to MR (Read, 2001). If the estimate is good, appropriate weight is placed on the agreement of reflections at different resolutions and it is not necessary to apply arbitrary resolution cutoffs. The r.m.s.d. is introduced into the likelihood targets via the parameter A, PðEo; EcÞ 1⁄4 À. Ais a function of resolution (measured by s = 1/d, the absolute value of the diffraction vector) that combines the effects of positional errors of the atoms in the model (the doi:10.1107/S0907444913023512 2209 research papers r.m.s.d.) and the completeness of the model fP, i.e. the ratio between the scattering power of the model and of the crystal (Read, 1986; Srinivasan & Ramachandran, 1966). Ignoring the effects of bulk solvent, A can be expressed in the simple form given in (2),

Objectives

Methods

Results

Conclusion