the advent of structural genomics initiatives has led to an increase in the number of protein 3d structures and hence there is a growing need for novel analysis tools ( 13 ) .
maintenance of the various analysis programs on changing computer platforms is becoming a problem for many users .
the protein tools page at icgeb is a collection of locally developed methods designed to assist users in the analysis of 3d structures .
therefore , they are particularly suited for online use and for large - scale data management . all the three servers described here
were written as standard c programs with php front end and run on a beowulf type linux cluster .
the servers accept the protein data bank ( pdb ) files ( 4 ) , a description of the input / output options as well as the underlying theory is provided in the form of online help files .
the cx server is a visualization tool designed to highlight protruding atoms within a protein structure .
identification of protruding , or highly convex regions in proteins is relevant to the analysis of interfaces in protein 
protein complexes , in the prediction of limited proteolysis cleavage sites and in the identification of possible antigenic determinant regions .
cx ( 13,5 ) calculates the ratio between the external volume and the volume occupied by the protein within a sphere centered at every protein atom .
atoms in protruding regions will have a high ratio between the external and the internal volume , i.e. a high cx protrusion index . for protein structures
only two independent parameters are used by cx : the average atomic volume and the sphere radius . the default value for the average atomic volume used by cx
given the approximate nature of the method and its purposes , slight variations in the average atomic volume do not affect the results in a remarkable way .
smaller values of r will make cx more sensitive to the local environment , whereas larger values will make it more sensitive to the global shape of the protein .
the default radius used by cx ( 10  ) is a good compromise to highlight both backbone and side chain protruding atoms in most applications ( figure 1a ) .
the dpx server is designed to facilitate the analysis of buried atoms within the protein interior .
parameters , such as the solvent accessible area ( 6 ) and the occluded surface , can not distinguish buried residues that are close to the protein surface from those that are deep inside the protein core .
depth defined as the distance between a protein atom and the nearest water molecule surrounding the protein ( 7 ) was found to be a useful descriptor of the protein interior .
depth correlates better than solvent accessibility not only with amide h / d exchange rates for several proteins , but also with the difference in the thermodynamic stability of proteins containing cavity - creating mutations and with the change in the free energy formation of protein  protein complexes ( 8) .
we have developed the dpx index defined as the distance (  ) of a non - hydrogen buried atom from its closest solvent accessible protein neighbor ( 9,10 ) where buried and accessible atoms are identified using the rolling sphere algorithm . although some information is lost for surface atoms ( all solvent exposed atoms have dpx = 0 by default ) , the depth calculation is very fast because neither water molecules nor surface dots are explicitly considered .
the only parameter that can be varied is the radius of the probe sphere , for which the default value is set to 1.4  ( figure 1b ) .
both cx and dpx read atom lines from a pdb file submitted by the user .
non - standard residues , cofactors , metal ions and water molecules described in hetatm lines are not taken into account .
each chain in the pdb file is treated as an independent molecule but the results are written into a single output file in the pdb format , in which the cx or dpx values are written in place of the atomic displacement parameters ( b - factors ) .
the output file can thus be displayed using molecular graphics programs [ e.g. rasmol ( 11 ) and swiss - pdbviewer ( 12 ) ] , and atoms colored according to their cx ( or dpx ) value .
the pride server is designed to compare the fold ( backbone conformation ) of protein structures [ for a review , see carugo and pongor ( 2 ) and the database issue 2005 of nucleic acids research for current references ] .
pride is based on comparing distributions of intramolecular cc distances using a standard statistical process , contingency table analysis which gives a probability of identity or pride score ( 13 ) . for the calculation ,
c(i + n ) distance distributions ( 3 < n < 30 ) and the final pride score for two protein structures is the average calculated from the results of the 28 comparisons ( 0  pride  1 ) .
the calculation is extremely fast , so pairwise as well as multiple comparisons can be compared online . as pride
is a metric , it can be used to cluster and classify protein 3d structures through standard cluster analysis methods .
as the calculation is based only on the c atoms , the input files may contain only the c lines .
its output contains not only the final pride score , but also the values it was derived from as well as a graphic representation of the underlying histograms . in case the pride cluster option is used to analyze n protein 3d structures ( presented as concatenated pdb files ) , the server provides three , easily downloadable output files : ( i ) the n  n square matrix where each i - thj - th element is the distance , defined as 1-pride , between the i - th and the j - th protein 3d structures ; ( ii ) the dendrogram that summarizes a cluster analysis performed using the neighbor program of the phylip software suite by applying the neighbor - joining criterion for cluster merging ( figure 1 ) ; and ( iii ) a newick - format tree description that allows one to build its own dendrograms with the help of programs , such as njplot ( ) and treeview ( ) . in case the pride / scan option is used , the database search option of the server makes it possible to compare a 3d structure with the folds of the cath database ( 14 ) .
the search results are presented as a ranked list , and according to the statistical evaluation , in over 99.5 of the cases the most similar structure points to the correct topology group .
the protein tools server . ( a ) title page [ the sbase ( 15 ) , fthom ( 16 ) and p450 ( 17 ) services have been described elsewhere ] .
bottom : structure of the human histone lysine n - methyltransferase set7/9 complexed with a histone peptide and s - adenosyl - l - homocysteine ( sah ) , pdb : 1o9s .
the enzyme is shown as ribbons , the peptide as sticks and sah as a cpk model using ; the structure is colored according to the cx values , calculated using a sphere radius of 8  .
( d ) output of the dpx server rendered with rasmol ( 5 ) , the cpk model of the enzyme is shown in slab mode in the same orientation as in the left panel , and atoms colored according to their dpx values .
 the www servers at   are dedicated to the analysis of protein 3d structures submitted by the users as the protein data bank ( pdb ) files . 
 cx computes an atomic protrusion index that makes it possible to highlight the protruding atoms within a protein 3d structure . 
 dpx calculates a depth index for the buried atoms and makes it possible to analyze the distribution of buried residues . 
 cx and dpx return pdb files containing the calculated indices that can then be visualized using standard programs , such as swiss - pdbviewer and rasmol . 
 pride compares 3d structures using a fast algorithm based on the distribution of inter - atomic distances . 
 the options include pairwise as well as multiple comparisons , and fold recognition based on searching the cath fold database . 
INTRODUCTION
Figures and Tables