02259nas a2200253   4500008004100000022001400041245012000055210006900175260005700244300000700301490000700308520138300315653000801698653001701706653000901723653002601732653001801758653002201776653001401798100002201812700003001834700001501864856012601879       2016                        eng d  a1610-294000aProbing the ATP-induced conformational flexibility of the PcrA helicase protein using molecular dynamics simulation0 aProbing the ATPinduced conformational flexibility of the PcrA he  a233 SPRING ST, NEW YORK, NY 10013 USAbSPRINGERcMAR  a540 v223 a<p>Helicases are enzymes that unwind double-stranded DNA (dsDNA) into its single-stranded components. It is important to understand the binding and unbinding of ATP from the active sites of helicases, as this knowledge can be used to elucidate the functionality of helicases during the unwinding of dsDNA. In this work, we investigated the unbinding of ATP and its effect on the active-site residues of the helicase PcrA using molecular dynamic simulations. To mimic the unbinding process of ATP from the active site of the helicase, we simulated the application of an external force that pulls ATP from the active site and computed the free-energy change during this process. We estimated an energy cost of similar to 85 kJ/mol for the transformation of the helicase from the ATP-bound state (1QHH) to the ATP-free state (1PJR). Unbinding led to conformational changes in the residues of the protein at the active site. Some of the residues at the ATP-binding site were significantly reoriented when the ATP was pulled. We observed a clear competition between reorientation of the residues and energy stabilization by hydrogen bonds between the ATP and active-site residues. We also checked the flexibility of the PcrA protein using a principal component analysis of domain motion. We found that the ATP-free state of the helicase is more flexible than the ATP-bound state.</p>10aATP10aDNA helicase10aPcrA10aResidue reorientation10aTranslocation10aUmbrella sampling10aUnwinding1 aMhashal, Anil, R.1 aChoudhury, Chandan, Kumar1 aRoy, Sudip  uhttps://library.ncl.res.in/content/probing-atp-induced-conformational-flexibility-pcra-helicase-protein-using-molecular-1