BACKGROUND
protein-nucleic acid interactions play an important role in many biological activities.
site-specific dna-binding proteins or transcription factors  play important roles in gene regulations by forming protein complexes  <cit> .
these protein-dna complexes may bind alone or in combination near the genes whose expression they control  <cit> .
for example, dna-binding proteins may regulate the expression of a target gene  <cit> , so protein-dna interactions are important for dna replication, transcription and gene regulations in general.
protein-rna interactions also have important roles in a wide variety of gene expression  <cit> .
for instance, ribonucleoprotein particles  bind to rna in the post-transcriptional regulation of gene expression  <cit> , and trnas bind to aminoacyl-trna synthetases to properly translate the genetic code into amino acids  <cit> .
as protein and rna mutually interact, rna-binding proteins are essential molecules in degradation, localization, regulating rna splicing, rna metabolism, stability, translation, and transport  <cit> .
therefore, identification of amino acids involved in dna/rna binding or nucleotides involved in amino acid binding is important for understanding of the mechanism of gene regulations.
as the number of structures of protein-dna/rna complexes that have been resolved has been increased plentifully for the past few years, a huge amount of structure data is available at several databases  <cit> .
however, the data on the binding sites between proteins and nucleic acids is not readily available from the structure data, which consist mostly of the three-dimensional coordinates of the atoms in the complexes.
a recent database called the protein-rna interface database   <cit>  provides the information on protein-rna interfaces by showing interacting amino acids and ribonucleotides in the primary sequences.
however, it does not provide the binding sites on the interacting partners of the amino acids and ribonucleotides in protein-rna interfaces.
in this study we performed wide analysis of the structures of protein-dna/rna complexes and built a database called dbbp .
the database shows hydrogen-bonding interactions between proteins and nucleic acids at an atomic level, which is not readily available in any other databases, including the protein data bank   <cit> .
the binding pairs of hydrogen bonds provided by the database will help researchers determine dna  binding sites in proteins and protein binding sites in dna or rna molecules.
it can also be used as a valuable resource for developing a computational method aiming at predicting new binding sites in proteins or nucleic acids.
the rest of the paper presents the structure and interface of the database.
materials and methods
protein-dna/rna complexes
the protein-dna/rna complexes determined by x-ray crystallography were selected from pdb.
as of february,  <dig> there were  <dig>  protein-dna complexes and  <dig>  protein-rna complexes in pdb.
after extracting complexes with a resolution of  <dig>  Å or better,  <dig>  protein-dna complexes  and  <dig> protein-rna complexes  remained.
binding sites in protein-nucleic acid interactions
different studies  <cit>  have defined slightly different criteria for a binding site in protein-nucleic acid interactions.
for example, in rnabindr  <cit>  and bindn  <cit>  an amino acid with an atom within a distance of  <dig> Å from any other atom of a ribonucleotide was considered to be an rna-binding amino acid.
as for the criteria for a binding site between proteins and nucleic acids, we use a hydrogen bond , which is stricter than the distance criteria.
the locations of hydrogen atoms  were inferred from the surrounding atoms since hydrogen atoms are invisible in purely x-ray-derived structures.
h-bonds between proteins and nucleic acids were identified by finding all proximal atom pairs between h-bond donors  and acceptors  that satisfy the following the geometric criteria:  the hydrogen-acceptor  distance < <dig>  Å,  the donor-hydrogen-acceptor  angle >90°,  the contacts with the donor-acceptor  distance < <dig>  Å,  h-a-aa angle >90°, where aa is an acceptor antecedent.
these are the most commonly used criteria for h bonds.
in particular, the criteria of h-a distance < <dig>  Å and d-h-a angle >90° are essential for h bonds  <cit> .
if there is no h-bond within a protein-nucleic acid complex, we eliminated the complex from the data sets of ds <dig> and ds <dig>  as a result, we gathered  <dig>  protein-dna complexes  and  <dig> protein-rna complexes .
as an example, figure  <dig> shows three h-bonds between threonine  and cytosine  in a protein-rna complex   <cit> .
in protein-rna interactions, og <dig> and n of threonine can act as a hydrogen donor and og <dig> and o of threonine can act as a hydrogen acceptor.
n <dig>  n <dig>  o2′ and o3′ of cytosine can act as a hydrogen donor and n <dig>  o <dig>  o2′, o3′, o4′, o5′, op <dig> and op <dig> of cytosine can act as a hydrogen acceptor.
in this example, cytosine is the 8th nucleotide in rna chain r and threonine is the 224th amino acid in protein chain a. og <dig> of threonine donates hydrogen to o2′ of cytosine, og <dig> of threonine donates hydrogen to o3′ of cytosine, and o2' of cytosine donates hydrogen to og <dig> of threonine.
figure  <dig> shows the structure of the protein-rna complex .
the probability of binding amino acid
let p  be the probability that an amino acid is a binding site and p  be the probability that an amino acid is a non-binding site in protein-nucleic acid interactions .
p=dna/rna - binding amino acidsamino acids in protein - dna/rna complexes
p=dna/rna - non - binding amino acidsamino acids in protein - dna/rna complexes
then, the conditional probability p is the probability that the binding amino acid is a. likewise, the conditional probability p is the probability that the non-binding amino acid is a. equation  <dig> is the log-likelihood ratio of p and p.
p=pp
p=pp
log-likelihoodratio=log2pp
RESULTS
hydrogen bonds in protein-nucleic acid interactions
we obtained h-bonds from  <dig>  protein-dna complexes  and  <dig> protein-rna complexes  using hbplus  <cit>  with the h-bond criteria: ha¯< <dig> a∘, ∠dha >90°, da¯< <dig> a∘.
there are a total of  <dig>  h-bonds in protein-dna complexes and  <dig>  h-bonds in protein-rna complexes.
table  <dig> shows the number of atoms, which are occurrences in h-bonds of amino acids.
in the  <dig>  h-bonds of protein-dna complexes, there are  <dig>  hydrogen donors and  <dig>  hydrogen acceptors in amino acids.
in the  <dig>  h-bonds of protein-rna complexes, there are  <dig>  hydrogen donors and  <dig>  hydrogen acceptors in amino acids.
table  <dig> shows the number of atoms, which are occurrences in h-bonds of nucleotides.
in the  <dig>  h-bonds of protein-dna complexes, there are  <dig>  hydrogen donors and  <dig>  hydrogen acceptors in dnas.
in the  <dig>  h-bonds of protein-rna complexes, there are  <dig>  hydrogen donors and  <dig>  hydrogen acceptors in rnas.
if an atom of dna acts as a hydrogen acceptor, an atom of protein should be a hydrogen donor.
hence, the number of dna acceptors  is the same as the number of protein donors , and the number of dna donors  is the same as the number of protein acceptors .
likewise, the number of rna acceptors  is the same as the number of protein donors  and the number of rna donors  is the same as the number of protein acceptors .
web interface
dbbp shows binding pairs at various levels, from the atomic level to the residue level.
when it shows detailed information on h-bonds, it shows the donors and acceptors of each h-bond.
a same type of atom can play a role of hydrogen donor or acceptor depending on the context.
we generated xml files for binding sites of protein-dna/rna complexes.
users of the database can access the xml file via pdb id.
CONCLUSIONS
from an extensive analysis of the structure data of protein-dna/rna complexes extracted from pdb, we have identified hydrogen bonds .
analysis of the large amount of structure data for h-bonds is labor-intensive, yet provides useful information for studying protein-nucleic acid interactions.
the protein-dna complexes contain  <dig>  h-bonds, which have  <dig>  hydrogen acceptors  and  <dig>  hydrogen donors  in amino acids, and  <dig>  ha and  <dig>  hd in nucleotides.
the protein-rna complexes contain  <dig>  h-bonds, which have  <dig>  ha and  <dig>  hd in amino acids, and  <dig>  ha and  <dig>  hd in nucleotides.
using the data of h-bonding interactions, we developed a database called dbbp .
dbbp provides the detailed information of h-bonding interactions between proteins and nucleic acids at various levels.
such information is not readily available in any other databases, including pdb, but will help researchers determine dna  binding sites in proteins and protein binding sites in dna or rna molecules.
it can also be used as a valuable resource for developing a computational method aiming at predicting new binding sites in proteins or nucleic acids.
the database is available at http://bclab.inha.ac.kr/dbbp.
authors' contributions
byungkyu park implemented the databse and prepared the first draft of the manuscript.
hyungchan kim drew figures and prepared the manuscript together.
kyungsook han supervised the work and rewrote the manuscript.
all authors read and approved the final manuscript.

 protein-nucleic acid interactions play an important role in many biological activities. site-specific dna-binding proteins or transcription factors play important roles in gene regulations by forming protein complexes. these protein-dna complexes may bind alone or in combination near the genes whose expression they control. for example, dna-binding proteins may regulate the expression of a target gene, so protein-dna interactions are important for dna replication, transcription and gene regulations in general. protein-rna interactions also have important roles in a wide variety of gene expression. for instance, ribonucleoprotein particles bind to rna in the post-transcriptional regulation of gene expression, and trnas bind to aminoacyl-trna synthetases to properly translate the genetic code into amino acids. as protein and rna mutually interact, rna-binding proteins are essential molecules in degradation, localization, regulating rna splicing, rna metabolism, stability, translation, and transport. therefore, identification of amino acids involved in dna/rna binding or nucleotides involved in amino acid binding is important for understanding of the mechanism of gene regulations. as the number of structures of protein-dna/rna complexes that have been resolved has been increased plentifully for the past few years, a huge amount of structure data is available at several databases. however, the data on the binding sites between proteins and nucleic acids is not readily available from the structure data, which consist mostly of the three-dimensional coordinates of the atoms in the complexes. a recent database called the protein-rna interface database provides the information on protein-rna interfaces by showing interacting amino acids and ribonucleotides in the primary sequences. however, it does not provide the binding sites on the interacting partners of the amino acids and ribonucleotides in protein-rna interfaces. in this study we performed wide analysis of the structures of protein-dna/rna complexes and built a database called dbbp. the database shows hydrogen-bonding interactions between proteins and nucleic acids at an atomic level, which is not readily available in any other databases, including the protein data bank. the binding pairs of hydrogen bonds provided by the database will help researchers determine dna binding sites in proteins and protein binding sites in dna or rna molecules. it can also be used as a valuable resource for developing a computational method aiming at predicting new binding sites in proteins or nucleic acids. the rest of the paper presents the structure and interface of the database. materials and methods protein-dna/rna complexes the protein-dna/rna complexes determined by x-ray crystallography were selected from pdb. as of february, there were protein-dna complexes and protein-rna complexes in pdb. after extracting complexes with a resolution of Å or better, protein-dna complexes and protein-rna complexes remained. binding sites in protein-nucleic acid interactions different studies have defined slightly different criteria for a binding site in protein-nucleic acid interactions. for example, in rnabindr and bindn an amino acid with an atom within a distance of Å from any other atom of a ribonucleotide was considered to be an rna-binding amino acid. as for the criteria for a binding site between proteins and nucleic acids, we use a hydrogen bond, which is stricter than the distance criteria. the locations of hydrogen atoms were inferred from the surrounding atoms since hydrogen atoms are invisible in purely x-ray-derived structures. h-bonds between proteins and nucleic acids were identified by finding all proximal atom pairs between h-bond donors and acceptors that satisfy the following the geometric criteria: the hydrogen-acceptor distance < Å, the donor-hydrogen-acceptor angle >90°, the contacts with the donor-acceptor distance < Å, h-a-aa angle >90°, where aa is an acceptor antecedent. these are the most commonly used criteria for h bonds. in particular, the criteria of h-a distance < Å and d-h-a angle >90° are essential for h bonds. if there is no h-bond within a protein-nucleic acid complex, we eliminated the complex from the data sets of ds and ds as a result, we gathered protein-dna complexes and protein-rna complexes. as an example, figure shows three h-bonds between threonine and cytosine in a protein-rna complex. in protein-rna interactions, og and n of threonine can act as a hydrogen donor and og and o of threonine can act as a hydrogen acceptor. n n o2′ and o3′ of cytosine can act as a hydrogen donor and n o o2′, o3′, o4′, o5′, op and op of cytosine can act as a hydrogen acceptor. in this example, cytosine is the 8th nucleotide in rna chain r and threonine is the 224th amino acid in protein chain a. og of threonine donates hydrogen to o2′ of cytosine, og of threonine donates hydrogen to o3′ of cytosine, and o2' of cytosine donates hydrogen to og of threonine. figure shows the structure of the protein-rna complex. the probability of binding amino acid let p be the probability that an amino acid is a binding site and p be the probability that an amino acid is a non-binding site in protein-nucleic acid interactions. p=dna/rna - binding amino acidsamino acids in protein - dna/rna complexes p=dna/rna - non - binding amino acidsamino acids in protein - dna/rna complexes then, the conditional probability p is the probability that the binding amino acid is a. likewise, the conditional probability p is the probability that the non-binding amino acid is a. equation is the log-likelihood ratio of p and p. p=pp p=pp log-likelihoodratio=log2pp  hydrogen bonds in protein-nucleic acid interactions we obtained h-bonds from protein-dna complexes and protein-rna complexes using hbplus with the h-bond criteria: ha¯< a∘, ∠dha >90°, da¯< a∘. there are a total of h-bonds in protein-dna complexes and h-bonds in protein-rna complexes. table shows the number of atoms, which are occurrences in h-bonds of amino acids. in the h-bonds of protein-dna complexes, there are hydrogen donors and hydrogen acceptors in amino acids. in the h-bonds of protein-rna complexes, there are hydrogen donors and hydrogen acceptors in amino acids. table shows the number of atoms, which are occurrences in h-bonds of nucleotides. in the h-bonds of protein-dna complexes, there are hydrogen donors and hydrogen acceptors in dnas. in the h-bonds of protein-rna complexes, there are hydrogen donors and hydrogen acceptors in rnas. if an atom of dna acts as a hydrogen acceptor, an atom of protein should be a hydrogen donor. hence, the number of dna acceptors is the same as the number of protein donors, and the number of dna donors is the same as the number of protein acceptors. likewise, the number of rna acceptors is the same as the number of protein donors and the number of rna donors is the same as the number of protein acceptors. web interface dbbp shows binding pairs at various levels, from the atomic level to the residue level. when it shows detailed information on h-bonds, it shows the donors and acceptors of each h-bond. a same type of atom can play a role of hydrogen donor or acceptor depending on the context. we generated xml files for binding sites of protein-dna/rna complexes. users of the database can access the xml file via pdb id.  from an extensive analysis of the structure data of protein-dna/rna complexes extracted from pdb, we have identified hydrogen bonds. analysis of the large amount of structure data for h-bonds is labor-intensive, yet provides useful information for studying protein-nucleic acid interactions. the protein-dna complexes contain h-bonds, which have hydrogen acceptors and hydrogen donors in amino acids, and ha and hd in nucleotides. the protein-rna complexes contain h-bonds, which have ha and hd in amino acids, and ha and hd in nucleotides. using the data of h-bonding interactions, we developed a database called dbbp. dbbp provides the detailed information of h-bonding interactions between proteins and nucleic acids at various levels. such information is not readily available in any other databases, including pdb, but will help researchers determine dna binding sites in proteins and protein binding sites in dna or rna molecules. it can also be used as a valuable resource for developing a computational method aiming at predicting new binding sites in proteins or nucleic acids. the database is available at http://bclab.inha.ac.kr/dbbp. authors' contributions byungkyu park implemented the databse and prepared the first draft of the manuscript. hyungchan kim drew figures and prepared the manuscript together. kyungsook han supervised the work and rewrote the manuscript. all authors read and approved the final manuscript. 
interaction of proteins with other molecules plays an important role in many biological activities. we analyzed the huge amount of structure data for the hydrogen bonding interactions between proteins and nucleic acids and developed a database called dbbp. analysis of the huge amount of structure data of protein-nucleic acid complexes is labor-intensive, yet provides useful information for studying protein-nucleic acid interactions. however, the information on the binding sites between proteins and nucleic acids is not readily available from the structure data since the data consists mostly of the three-dimensional coordinates of the atoms in the complexes. dbbp provides the detailed information of hydrogen-bonding interactions between proteins and nucleic acids at various levels from the atomic level to the residue level. the binding information can be used as a valuable resource for developing a computational method aiming at predicting new binding sites in proteins or nucleic acids. dbbp contains hydrogen bonds of protein-dna interactions and h-bonds of protein-rna interactions. as many structures of protein-dna complexes and protein-rna complexes have been determined in the past years, several databases have been constructed to provide structure data of the complexes.
 interaction of proteins with other molecules plays an important role in many biological activities. as many structures of protein-dna complexes and protein-rna complexes have been determined in the past years, several databases have been constructed to provide structure data of the complexes. however, the information on the binding sites between proteins and nucleic acids is not readily available from the structure data since the data consists mostly of the three-dimensional coordinates of the atoms in the complexes.  we analyzed the huge amount of structure data for the hydrogen bonding interactions between proteins and nucleic acids and developed a database called dbbp. dbbp contains hydrogen bonds of protein-dna interactions and h-bonds of protein-rna interactions.  analysis of the huge amount of structure data of protein-nucleic acid complexes is labor-intensive, yet provides useful information for studying protein-nucleic acid interactions. dbbp provides the detailed information of hydrogen-bonding interactions between proteins and nucleic acids at various levels from the atomic level to the residue level. the binding information can be used as a valuable resource for developing a computational method aiming at predicting new binding sites in proteins or nucleic acids. 28- july international conference on intelligent computing nanning, china 