BIOINFORMATICS ORIGINAL PAPER doi:10.1093/bioinformatics/btm480 Structural bioinformatics
This work uses a sampling method known as particle filtering to produce a set of all-atom protein models, and shows that this approach produces a more accurate model than three leading methods--Textal, Resolve and ARP/WARP--in terms of main chain completeness, sidechain identification and crystallographic R factor.
Abstract
MOTIVATION One bottleneck in high-throughput protein crystallography is interpreting an electron-density map, that is, fitting a molecular model to the 3D picture crystallography produces. Previously, we developed ACMI (Automatic Crystallographic Map Interpreter), an algorithm that uses a probabilistic model to infer an accurate protein backbone layout. Here, we use a sampling method known as particle filtering to produce a set of all-atom protein models. We use the output of ACMI to guide the particle filter's sampling, producing an accurate, physically feasible set of structures. RESULTS We test our algorithm on 10 poor-quality experimental density maps. We show that particle filtering produces accurate all-atom models, resulting in fewer chains, lower sidechain RMS error and reduced R factor, compared to simply placing the best-matching sidechains on ACMI's trace. We show that our approach produces a more accurate model than three leading methods--Textal, Resolve and ARP/WARP--in terms of main chain completeness, sidechain identification and crystallographic R factor. AVAILABILITY Source code and experimental density maps available at http://ftp.cs.wisc.edu/machine-learning/shavlik-group/programs/acmi/