You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
it is a labile protein which is comprised of 393 amino acids , folded and unstructured regions that function in a synergistic manner   and responsible for induction of cell cycle arrest or apoptosis based on the cellular damage , stress , and cell type . in cell cycle
, it acts as a transactivator that negatively regulates cell division by controlling a set of genes required for this process such as cyclin - dependent kinases , protein kinases , and cyclin - dependent inhibitors . in apoptosis , it is responsible for highly complex and sophisticated processes involving energy - dependent cascade of molecular events .
induction of apoptosis is mediated either by bax stimulation and antigen expression of fas or by repression of bcl-2 expression .
human hsp70 functions as atp - dependent molecular chaperone which plays a crucial role in proteins folding , assembly or disassembly of other protein structures , and protecting from cell stress [ 3 , 4 ] .
human hsp70 has 640 amino acids and is comprised of two structurally independent domains such as nucleotide binding domain ( nbd ) and c - terminal substrate binding domain ( sbd ) .
nbd ( residues 1380 ) is responsible for atpase activity while sbd ( residues 397641 ) plays the key role in binding of peptides and folding of nonnative polypeptides .
in addition , a hydrophobic linker of 13 residues ( 384396 ) that carries a highly conserved leucine - rich motif ( eevd ) is connected between nbd and sbd .
there has been evidence that the xenopus laevis p53 can bind to mammalian hsp70 protein .
the formation of p53-hsp70 complex might enhance stabilization of p53 in cancer cells , thus increasing killing efficiency of cancer cells .
however , the process of hsp70 molecular chaperone involved in the buffering of p53 conformation and activity is not clear up until now . in this study
, we have explored for the first time how the nbd interacts with p53 motif .
we then determined the binding affinity and stability of nbd - p53 motif complex structure through molecular docking and dynamics ( md ) simulation .
therefore , the results could help in designing the structure based drug hsp70 for cancer treatment .
the complete amino acid sequence of hspa1a was obtained from rcsb protein databank ( pdb : 1hjo ) .
the protein model was visualized using pymol software . currently , there is no tertiary structure of homo sapiens dna binding domain of p53 available in the protein database .
the complete amino acid sequence of dna binding domain of p53 was retrieved from uniprot ( uniprotkb : p04637 ) .
blastp against the rcsb protein databank was carried out to find a suitable template for homology modeling .
crystal structure of 1ycs was selected as a template based on maximum identity with high positives and lower gaps percentage .
the percentages of query coverage , sequence identity , positivity , and gap between the template and target protein were 100% , 100% , 100% , and 0% , respectively .
the three - dimensional structure of dna binding domain of p53 was built using easymodeller 2.1 software , the graphical user interface ( gui ) of modeller 9.10 , and the model was then viewed using pymol software . the three - dimensional model of the dna binding domain of p53 motif ( scmggmnr )
was created using the built three - dimensional model of dna binding domain of p53 as a template .
the gromacs package 4.6.3   adopting the gromos 53a6 force field parameter was employed to perform 50  ns md simulation for the p53 motif before blind docking with the nbd protein .
the three - dimensional model of nbd protein was used for molecular docking with the tertiary structure of p53 motif ( scmggmnr ) using autodock version 4.2 program . in the protein , nonpolar hydrogen atoms were merged and total kollman and gasteiger charge was added to the protein .
kollman and gasteiger partial charges were also assigned to the ligand and all torsions were allowed to rotate during docking .
the nbd and p53 motif were converted from the pdb format to the pdbqt format .
a grid box was used around the active site to cover the entire protein binding site and allow ligands to move freely ; and affinity maps of nbd ( 74  88  108 containing total grid points of 727575 ) were calculated by autogrid .
one hundred lamarckian genetic algorithm ( lga ) runs with default parameter settings were performed .
the largest docked conformations were clustered at rms of 1.0  nm and played according to the rank of the native autodock scoring function .
the interactions of complex nbd protein - p53 motif conformations including hydrogen bonds and bond lengths were analyzed . in the 50  ns md simulation , the docked complex of p53 motif with nbd protein was simulated using the gromacs package 4.6.3 adopting the gromos53a6 force field parameter .
we used a cubic box setting a minimal distance of 1.0 between the protein and edge of the box , which was then solvated using periodic boundary conditions and the spc ( simple point charge ) water model in this study .
the ligand topology file was generated using the prodrg server to include the heteroatom due to limitations of gromacs to parameterize the heteroatom group in the pdb file . to make the system neutral
the entire system for the nbd protein was minimized using 993 steps of steepest descent , respectively .
after energy minimization with particle - mesh ewald algorithm at every step , the system was then equilibrated at a constant temperature ( 303  k ) , volume , number of particles in system , and pressure ( 1  bar ) for 50  ps . under constant volume equilibration
moreover , under constant pressure equilibration , the temperature was controlled by berendsen weak coupling method and the pressure was maintained by parrinello - rahman barostat method .
after completion of the two equilibration phases , production of md simulation was conducted for 1  ns after taking away the position restraints . finally , the equilibrated structures were subjected to md simulations for 50  ns ( 50,000  ps ) with linear constrain ( lincs ) algorithm 2  fs time step to constrain all the bonds .
the nonbonded list was generated using an atom - based cut - off of 10   .
root mean square deviations ( rmsd ) , backbone atomic fluctuations ( rmsf ) , secondary structure , hydrogen bonds , and salt bridge between the protein and ligand in the docked complex during the simulation were analyzed through gromacs utilities g_rmsd , g_rmsf , do_dssp , g_hbond , and g_salt , respectively .

 homo sapiens hspa1a - p53 interaction was identified using string version 9.1 program .  
figure 1 shows that hspa1a either directly interacted with p53 or used intermediate stub1 to connect with p53 .
stub1 is stip1 homology and u - box containing protein 1 which modulates several chaperone complexes ' activity such as hsp70 , hsc70 , and hsp90 .
it has e3 ubiquitin - protein ligase activity and targets misfolded chaperone substrates towards proteasomal degradation .
it also mediates transfer of noncanonical short ubiquitin chains to hspa8 that have no effect on degradation of hspa8 .
, only two experimental studies demonstrated the detection of human hspa1a - p53 complex by affinity capture western assay and in vivo assay . in mammalian cancer lines ,
hspa1a was found to associate with p53 in the cytoplasm but the complex dissociates upon translocation of p53 into the nucleus .
both of the experimental results show that p53-hsp70 complex formation might be one of the mechanisms of stabilization of p53 protein resulting in its increased levels in potentially malignant and malignant tumors [ 14 , 15 ] . however , to date , the process of hsp70 molecular chaperone participating in the buffering of p53 conformation and activity is not known clearly , where p53 plays important role in inhibition of tumorigenesis . based on studies by fourie et al .
( 2004 ) , it has been described that hsp70 interacts with p53 dbd ( dna binding domain ) [ 1618 ] .
p53 dbd contains 191 amino acids ( from residue 102 to residue 292 ) . mutations usually occur in dbd .
this causes deactivation of p53 by destroying the ability of the protein to bind to its target dna sequences , thus preventing transcriptional activation of these genes .
for example , mutation of p53 dbd at residue 248 ( arginine ) distorts the protein structure .
there are three regions in p53 dbd such as region 1 ( from residue 113 to 226 ) which is required for interaction with fbx042 ; region 2 ( from residue 116 to 292 ) involved in interaction with ax1n1 ; and region 3 ( from residue 241 to 248 ) that interacts with the 53bp2 sh3 domain .
scmggmnr ( region 3 ) transmits antiproliferative signals through 53bp2 sh3 domain to antiapoptotic bcl2 family proteins ( bcl-2 , bcl - w , and bcl - xl ) .
therefore , molecular dynamics simulation and docking approaches have been used to determine the preferred sites , binding affinity , and stability of the hspa1a - p53 motif complex structure .
the docking analysis revealed that nbd had a strong bond with p53 motif due to negative and low binding energy ( 0.44  kcal / mol ) .
the total intermolecular energy of nbd - p53 motif complex was 9.9  kcal / mol .
other binding parameters of p53 motif such as electrostatic energy ( 3.70  kcal / mol ) , internal energy ( 4.23  kcal / mol ) , torsion energy ( 9.55  kcal / mol ) , unbounded extended energy ( 4.23  kcal / mol ) , cluster rms ( 0.0 ) , and reference rms ( 61.53 ) were also determined .
in addition , the nbd protein formed four hydrogen bonds with p53 motif ( figure 2 and table 1 ) .
the nbd - p53 motif complex was run for 50  ns molecular dynamics simulation .
the rmsd value of the protein - ligand complex model against the simulation period is shown in figure 3(a ) .
it can be seen that the nbd - p53 motif complex achieved a stable value at 45,000  ps ( 0.20  nm ) .
moreover , the rmsd value was less deviated throughout the 50  ns simulation time .
results from rmsf analysis show that all the residues in the protein structure fluctuated between 0.05 and 0.30  nm in the entire simulation period ( figure 3(b ) ) .
the nbd - p53 complex exhibited a high fluctuation up to 0.54  nm at residue 380 .
furthermore , salt bridges occurring between the nbd protein and p53 motif are demonstrated in figure 3(c ) .
the protein - ligand complex exhibited a stable distance of 2.50  nm throughout the simulation period .
the deviation in flexibility was further analyzed by the number of hydrogen bonds formed between the nbd protein and p53 motif during md simulation ( figure 3(d ) ) .
the hydrogen bond analysis revealed that nbd - p53 motif complex shows four intermolecular hydrogen bonds , which were determined throughout the simulation period .
at least 1 - 2 intermolecular hydrogen bonds were kept for the entire 50  ns trajectories , which inferred the stability of nbd - p53 motif complex .
in addition , history - independent hydrogen bond autocorrelation function was calculated between the protein and the ligand ( figure 3(e ) ) .
furthermore , the secondary structure also plays an essential role in stability of such a system .  
figure 3(f ) indicates that the alpha- , 5- , and 3-helixes were constant throughout the simulation period which infers that the protein - ligand complex structure was stable .
rmsd , rmsf , salt bridge , hydrogen bond , and secondary structure analyses have proven that the protein interaction between the nbd protein and p53 motif was stable .
in addition , nbd of hspa1a had a strong bond with p53 motif ( scmggmnr ) .
therefore , the current data would be highly encouraging for in vitro experiments of gene therapy in cancer treatment .
moreover , a better understanding of in silico interpretations of this protein structure will aid in the development of target - specific anticancer drugs for cancer treatment .
currently , protein interaction of homo sapiens nucleotide binding domain ( nbd ) of heat shock 70  kda protein ( pdb : 1hjo ) with p53 motif remains to be elucidated . the nbd - p53 motif complex enhances the p53 stabilization , thereby increasing the tumor suppression activity in cancer treatment . 
 therefore , we identified the interaction between nbd and p53 using string version 9.1 program . 
 then , we modeled the three - dimensional structure of p53 motif through homology modeling and determined the binding affinity and stability of nbd - p53 motif complex structure via molecular docking and dynamics ( md ) simulation . 
 human dna binding domain of p53 motif ( scmggmnr ) retrieved from uniprot ( uniprotkb : p04637 ) was docked with the nbd protein , using the autodock version 4.2 program . 
 the binding energy and intermolecular energy for the nbd - p53 motif complex were 0.44  kcal / mol and 9.90  kcal / mol , respectively . 
 moreover , rmsd , rmsf , hydrogen bonds , salt bridge , and secondary structure analyses revealed that the nbd protein had a strong bond with p53 motif and the protein - ligand complex was stable . thus , the current data would be highly encouraging for designing hsp70 structure based drug in cancer therapy .