03269nas a2200337   4500008004100000245010000041210006900141300001200210490000700222520201600229653008002245653005102325653005202376653014002428100001502568700001402583700001602597700002402613700001802637700001902655700001702674700001402691700002402705700001402729700001302743700001902756700001802775700001902793700001302812856010602825       2004                        eng d00aMODBASE, a database of annotated comparative protein structure models, and associated resources0 aMODBASE a database of annotated comparative protein structure mo  aD217-220 v323 aMODBASE (http://salilab.org/modbase) is a relational database of annotated comparative protein structure models for all available protein sequences matched to at least one known protein structure. The models are calculated by MODPIPE, an automated modeling pipeline that relies on the MODELLER package for fold assignment, sequence-structure alignment, model building and model assessment (http:/salilab.org/modeller). MODBASE uses the MySQL relational database management system for flexible querying and CHIMERA for viewing the sequences and structures (http://www.cgl.ucsf.edu/chimera/). MODBASE is updated regularly to reflect the growth in protein sequence and structure databases, as well as improvements in the software for calculating the models. For ease of access, MODBASE is organized into different data sets. The largest data set contains 1,26,629 models for domains in 659,495 out of 1,182,126 unique protein sequences in the complete Swiss-Prot/TrEMBL database (August 25, 2003); only models based on alignments with significant similarity scores and models assessed to have the correct fold despite insignificant alignments are included. Another model data set supports target selection and structure-based annotation by the New York Structural Genomics Research Consortium; e.g. the 53 new structures produced by the consortium allowed us to characterize structurally 24,113 sequences. MODBASE also contains binding site predictions for small ligands and a set of predicted interactions between pairs of modeled sequences from the same genome. Our other resources associated with MODBASE include a comprehensive database of multiple protein structure alignments (DBALI, http://salilab.org/dbali) as well as web servers for automated comparative modeling with MODPIPE (MODWEB, http://salilab. org/modweb), modeling of loops in protein structures (MODLOOP, http://salilab.org/modloop) and predicting functional consequences of single nucleotide polymorphisms (SNPWEB, http://salilab. org/snpweb).10aAmino Acid Sequence Animals Binding Sites *Computational Biology *Databases10aMolecular Molecular Sequence Data Polymorphism10aProtein Genomics Humans Internet Ligands Models10aSingle Nucleotide Protein Binding Protein Conformation Proteins/*chemistry/genetics Sequence Alignment Software User-Computer Interface1 aPieper, U.1 aEswar, N.1 aBraberg, H.1 aMadhusudhan, M., S.1 aDavis, F., P.1 aStuart, A., C.1 aMirkovic, N.1 aRossi, A.1 aMarti-Renom, M., A.1 aFiser, A.1 aWebb, B.1 aGreenblatt, D.1 aHuang, C., C.1 aFerrin, T., E.1 aSali, A.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1468139802302nas a2200205   4500008004100000245012700041210006900168300001100237490000700248520137200255653006101627653007901688653013001767100001701897700002401914700001801938700001301956700002101969856010601990       2004                        eng d00aStructure-based assessment of missense mutations in human BRCA1: implications for breast and ovarian cancer predisposition0 aStructurebased assessment of missense mutations in human BRCA1 i  a3790-70 v643 aThe BRCA1 gene from individuals at risk of breast and ovarian cancers can be screened for the presence of mutations. However, the cancer association of most alleles carrying missense mutations is unknown, thus creating significant problems for genetic counseling. To increase our ability to identify cancer-associated mutations in BRCA1, we set out to use the principles of protein three-dimensional structure as well as the correlation between the cancer-associated mutations and those that abolish transcriptional activation. Thirty-one of 37 missense mutations of known impact on the transcriptional activation function of BRCA1 are readily rationalized in structural terms. Loss-of-function mutations involve nonconservative changes in the core of the BRCA1 C-terminus (BRCT) fold or are localized in a groove that presumably forms a binding site involved in the transcriptional activation by BRCA1; mutations that do not abolish transcriptional activation are either conservative changes in the core or are on the surface outside of the putative binding site. Next, structure-based rules for predicting functional consequences of a given missense mutation were applied to 57 germ-line BRCA1 variants of unknown cancer association. Such a structure-based approach may be helpful in an integrated effort to identify mutations that predispose individuals to cancer.10aBRCA1 Genetic Predisposition to Disease Humans *Mutation10aBRCA1 Protein/*chemistry/genetics Breast Neoplasms/*genetics Female *Genes10aMissense Ovarian Neoplasms/*genetics Pedigree Protein Conformation Structure-Activity Relationship Transcriptional Activation1 aMirkovic, N.1 aMarti-Renom, M., A.1 aWeber, B., L.1 aSali, A.1 aMonteiro, A., N.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1517298501823nas a2200289   4500008004100000245006600041210006600107300001200173490000700185520083500192653004601027653002001073653011301093653003201206100001401238700001301252700001701265700001401282700001801296700001501314700001901329700002401348700002401372700001801396700001301414856010601427       2003                        eng d00aTools for comparative protein structure modeling and analysis0 aTools for comparative protein structure modeling and analysis  a3375-800 v313 aThe following resources for comparative protein structure modeling and analysis are described (http://salilab.org): MODELLER, a program for comparative modeling by satisfaction of spatial restraints; MODWEB, a web server for automated comparative modeling that relies on PSI-BLAST, IMPALA and MODELLER; MODLOOP, a web server for automated loop modeling that relies on MODELLER; MOULDER, a CPU intensive protocol of MODWEB for building comparative models based on distant known structures; MODBASE, a comprehensive database of annotated comparative models for all sequences detectably related to a known structure; MODVIEW, a Netscape plugin for Linux that integrates viewing of multiple sequences and structures; and SNPWEB, a web server for structure-based prediction of the functional impact of a single amino acid substitution.10aAmino Acid *Software *Structural Homology10aInternet Models10aMolecular Protein Folding Proteins/chemistry Reproducibility of Results Sequence Alignment Sequence Homology10aProtein Systems Integration1 aEswar, N.1 aJohn, B.1 aMirkovic, N.1 aFiser, A.1 aIlyin, V., A.1 aPieper, U.1 aStuart, A., C.1 aMarti-Renom, M., A.1 aMadhusudhan, M., S.1 aYerkovich, B.1 aSali, A.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12824331