research papers 2200 Reddy et al.  The TB Structural Genomics Bias Removal Web Service Acta Cryst. (2003). D59, 2200±2210 Acta Crystallographica Section D Biological Crystallography ISSN 0907-4449 Effective electron-density map improvement and structure validation on a Linux multi-CPU web cluster: The TB Structural Genomics Consortium Bias Removal Web Service Vinod Reddy, a Stanley M. Swanson, a Brent Segelke, b Katherine A. Kantardjieff, c James C. Sacchettini a and Bernhard Rupp a,b * a Biochemistry and Biophysics Department, Texas A&M University, 2128 TAMU, College Station, TX 77843-2128, USA, b Macro- molecular Crystallography and Structural Genomics Group, Lawrence Livermore National Laboratory, University of California, Livermore, CA 94551, USA, and c W. M. Keck Foundation Center for Molecular Structure, Department of Chemistry and Biochemistry, California State University Fullerton, 800 North State College Boulevard, Fullerton, CA 92834-6866, USA Correspondence e-mail: br@llnl.gov # 2003 International Union of Crystallography Printed in Denmark ± all rights reserved Anticipating a continuing increase in the number of structures solved by molecular replacement in high-throughput crystallo- graphy and drug-discovery programs, a user-friendly web service for automated molecular replacement, map improve- ment, bias removal and real-space correlation structure validation has been implemented. The service is based on an ef®cient bias-removal protocol, Shake&wARP, and imple- mented using EPMR and the CCP4 suite of programs, combined with various shell scripts and Fortran90 routines. The service returns improved maps, converted data ®les and real-space correlation and B-factor plots. User data are uploaded through a web interface and the CPU-intensive iteration cycles are executed on a low-cost Linux multi-CPU cluster using the Condor job-queuing package. Examples of map improvement at various resolutions are provided and include model completion and reconstruction of absent parts, sequence correction, and ligand validation in drug-target structures. Received 18 July 2003 Accepted 12 September 2003 1. Introduction The number of structures obtained by molecular replacement (MR) is expected to grow rapidly in coming years both in academic laboratories and in pharmaceutical structure-based drug-discovery efforts (Blundell et al., 2001). The increasing accessibility of powerful molecular-replacement programs and the increasing availability of search models owing to the discovery of novel folds by public and commercial structural genomics efforts (Norvell & Zapp-Machalek, 2000) are major contributing factors. An estimate of structures solved in a commercial structural genomics effort indicates that about 70% of all structures processed were solved by MR, and in drug-discovery efforts the numbers may be even higher (Kissinger et al., 2001). Anticipating a corresponding need for map improvement and electron-density-based structure validation, we present an effective easy-to-use web service for map improvement, phase-bias removal and rapid assessment of local model quality, which complements geometry-based structure- validation programs such as WHAT-IF (Vriend, 1990) and PROCHECK (Laskowski et al., 1993). The protocol, Shake&wARP, achieves effective bias removal using a modi- ®ed wARP (Perrakis et al. , 1997) procedure and is imple- mented using the CCP4 suite (Collaborative Computational Project, Number 4, 1994) of programs, various shell scripts and Fortran90 applets executable in parallel mode on multiple CPUs. Shake&wARP differs in details and choice of para- meters from the routines distributed with wARP, most notably