ProQM-resample: Improved model quality assessment for membrane proteins by limited conformational sampling

Abstract

Summary: Model Quality Assessment Programs (MQAPs) are used to predict the quality of modeled protein structures. These usually use two approaches: methods using consensus of many alternative models and methods requiring only a single model to do its prediction. The consensus methods are useful to improve overall accuracy; however, they frequently fail to pick out the best possible model and cannot be used to generate and score new structures. Single-model methods, on the other hand, do not have these inherent shortcomings and can be used to both sample new structures and improve existing consensus methods. Here, we present ProQM-resample, a membrane protein-specific single-model MQAP, that couples side-chain resampling with MQAP rescoring by ProQM to improve model selection. The side-chain resampling is able to improve side-chain packing for 96% of all models, and improve model selection by 24% as measured by the sum of the Z-score for the first-ranked model (from 25.0 to 31.1), even better than the state-of-the-art consensus method Pcons. The improved model selection can be attributed to the improved side-chain quality, which enables the MQAP to rescue good backbone models with poor side-chain packing. Availability and implementation: http://proqm.wallnerlab.org/download/. © The Author 2014.