thermodynamic database for proteins and mutants ( protherm ) and thermodynamic database for protein  nucleic acid interactions ( pronit )
are two comprehensive , integrated databases that document experimentally determined thermodynamic parameters published in the literature . both protherm ( 14 ) and pronit ( 5 )
include several thermodynamic parameters along with sequence and structural information , experimental methods and conditions , and literature information .
recent years have seen tremendous progress in studies on proteins owing to the development of various experimental methods to analyze proteins at the genome scale .
the correlation between structure and thermodynamics of these key molecules provides valuable insights into the way in which they function . even though the information is available in scientific journals , books ( 6,7 ) and literature databases , retrieving useful , specific data from these resources
our major goal in developing these databases is to provide the scientific community a single , comprehensive data repository , where all the thermodynamic data related to protein stability and protein  nucleic acid interactions are available .
the availability of such thermodynamic databases would be a valuable resource for understanding the protein folding mechanism , protein stability , molecular recognition and gene expressions .
this can lead to a wide spectrum of applications such as developing algorithms / methods for prediction systems , protein engineering and quantitative simulation of gene regulatory networks .
the thermodynamic data available in protherm and pronit are widely used by researchers to study the underlying mechanisms of protein stability upon mutations and protein  nucleic acid interactions ( see the reference sections on both the websites ) .
this paper describes the major updates and enhancements to these databases for the last few years .
both the databases contain information on protein , mutational information , experimental methods and conditions , several thermodynamic parameters and literature information .
previous publications ( 15 ) explain in detail the content and organization of the databases .
protherm and pronit are implemented in 3dinsight ( 8) , a relational database system for structure , function and property of biomolecules .
this facilitates more efficient search and retrieval of data by flexible queries , and enables users to gain insight into the relationship among structure , thermodynamics and function of proteins .
we have been collecting the thermodynamic data from published original articles , by searching the pubmed literature database with a combination of specific terms , as well as by searching online journals probably containing thermodynamic data .
the input data are checked automatically by checking programs and also manually to avoid errors .
then , we upload the data first to a test site , where expert curators check and verify the data . after this checking ,
, an email notification for each input entry is sent to the corresponding author , which enables the authors to check their own data and thereby improve the data validation .
we update both the databases frequently . the current release , protherm 5.0 contains 17  113 entries from 771 proteins , retrieved from 1497 scientific articles , which is 20% increase in data from the last version ( 4 ) . currently , the numbers of data for wild - type proteins , single , double and multiple mutants are 7014 , 8202 , 1277 and 620 , respectively . based on the solvent accessibility of mutants ,
4426 mutations are buried , 2687 partially buried and 2751 exposed . in terms of secondary structures , 3993 mutations are in helix , 2622 in strand , 1227 in turn and 2467 in coil regions .
majority of data are obtained from cd ( 6825 ) and dsc ( 5294 ) experiments followed by fluorescence ( 3628 ) .
further , 10  154 data are obtained by thermal denaturation , 3890 and 2796 data from gdnhcl and urea denaturation , respectively .
there are 158 different dna - binding proteins with 3489 wild - type entries and 1411 mutant entries .
majority of data are obtained by gel shift ( 1316 ) , fluorescence ( 1143 ) and filter binding ( 1053 ) , followed by calorimetry ( 727 ) , surface plasmon resonance ( 185 ) and footprinting ( 168 ) .
although proteins from a variety of organisms are present in pronit , majority of interaction data are from escherichia coli proteins ( 1625 ) followed by mus musculus ( 637 ) and homo sapiens ( 569 ) .
thus , we try to provide link from thermodynamic data in protherm to structural information .
so far , protherm data are connected to sequence and structural information of proteins through 3dinsight .
we have added a new cross - link between protherm and sting ( 9 ) , a comprehensive analysis tool for proteins with many structural descriptors . for given protein mutations searched within sting ,
conversely , all the protherm data with available protein structure have pointers to the corresponding sting entry with detailed structural information .
this cross - link will greatly facilitate the analysis of structure  thermodynamic relationship of proteins .
the protherm page also provides cross - reference tables necessary for creating cross - links with pdb ( 10 ) , pir ( 11 ) and swiss - prot ( 12 ) databases .
we have also added several new features in the search interface to make the search more efficient and convenient . in the current release of pronit 2.0 ,
we have included 200 protein  rna interaction data . to facilitate the retrieval of data based on dna and rna separately
, we have added a new field called type_nuc , where we provide the information about whether the nucleic acid sequence is dna ( single - stranded dna , ssdna , or double - stranded dna , dsdna ) or rna .
furthermore , a search option is added to retrieve data based on ssdna , dsdna or rna .
hence , we have added a new field , synonyms , in order to address this problem .
other additions of field are the swissprot i d of the protein and  related_entries , which provides the list of entries that contain data from the same paper ( the original paper usually contains multiple data and they are entered in different entries ) .
we also provide a link to all homologous pdb codes with sequence identity of > 95% . also , display options and sorting options are significantly improved .
we have supplied the lists of pronit entries , protein names , protein sources , pdb code , ndb codes ( 13 ) , authors and references in the advanced search page , along with a new query help page to help users for easy retrieval of the data .
several entries are deleted because of duplication , co - operative binding and so on , and the database entries are now renumbered . a mapping table , which relates the old and new entry numbers , is provided to help old users of pronit .
the users of protherm and pronit are requested to cite the references ( 4 ) and ( 5 ) , respectively , in their publication including the above urls .
users who use both the databases for their work may cite this article in their publications .
suggestions and other materials for inclusion in the databases are welcome and should be sent to either protherm@rtcmain.bse.kyutech.ac.jp or pronit@rtcmain.bse.kyutech.ac.jp .
 protherm and pronit are two thermodynamic databases that contain experimentally determined thermodynamic parameters of protein stability and protein  nucleic acid interactions , respectively . the current versions of both the databases have considerably increased the total number of entries and enhanced search interface with added new fields , improved search , display and sorting options . as on september 2005 
 , protherm release 5.0 contains 17  113 entries from 771 proteins , retrieved from 1497 scientific articles ( 20% increase in data from the previous version ) . 
 pronit release 2.0 contains 4900 entries from 273 research articles , representing 158 proteins . 
 both databases can be queried using www interfaces . both quick 
 search and advanced search are provided on this web page to facilitate easy retrieval and display of the data from these databases . 
 protherm is freely available online at   and pronit at . 
INTRODUCTION
CONTENT, ORGANIZATION AND DATA COLLECTION
DATABASE STATISTICS
NEW FEATURES
CITATION AND AVAILABILITY
Figures and Tables