Standard free energy of releasing a localized water molecule from the binding pockets of proteins: double-decoupling method. Export

@article{citeulike:771712, abstract = {Localized water molecules in the binding pockets of proteins play an important role in noncovalent association of proteins and small drug compounds. At times, the dominant contribution to the binding free energy comes from the release of localized water molecules in the binding pockets of biomolecules. Therefore, to quantify the energetic importance of these water molecules for drug design purposes, we have used the double-decoupling approach to calculate the standard free energy of tying up a water molecule in the binding pockets of two protein complexes. The double-decoupling approach is based on the underlying principle of statistical thermodynamics. We have calculated the standard free energies of tying up the water molecule in the binding pockets of these complexes to be favorable. These water molecules stabilize the protein-drug complexes by interacting with the ligands and binding pockets. Our results offer ideas that could be used in optimizing protein-drug interactions, by designing ligands that are capable of targeting localized water molecules in protein binding sites. The resulting free energy of ligand binding could benefit from the potential free energy gain accompanying the release of these water molecules. Furthermore, we have examined the theoretical background of the double-decoupling method and its connection to the molecular dynamics thermodynamic integration techniques.}, address = {Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0365, USA. dhamelbe@mccammon.ucsd.edu}, author = {Hamelberg, D. and McCammon, J. A.}, citeulike-article-id = {771712}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/ja0377908}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/ja0377908}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/15198616}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=15198616}, day = {23}, doi = {10.1021/ja0377908}, issn = {0002-7863}, journal = {J Am Chem Soc}, keywords = {water-ref}, month = {June}, number = {24}, pages = {7683--7689}, posted-at = {2006-07-24 20:11:45}, priority = {2}, title = {Standard free energy of releasing a localized water molecule from the binding pockets of proteins: double-decoupling method.}, url = {http://dx.doi.org/10.1021/ja0377908}, volume = {126}, year = {2004} }

TY - JOUR ID - citeulike:771712 L3 - citeulike-article-id:771712 N2 - Localized water molecules in the binding pockets of proteins play an important role in noncovalent association of proteins and small drug compounds. At times, the dominant contribution to the binding free energy comes from the release of localized water molecules in the binding pockets of biomolecules. Therefore, to quantify the energetic importance of these water molecules for drug design purposes, we have used the double-decoupling approach to calculate the standard free energy of tying up a water molecule in the binding pockets of two protein complexes. The double-decoupling approach is based on the underlying principle of statistical thermodynamics. We have calculated the standard free energies of tying up the water molecule in the binding pockets of these complexes to be favorable. These water molecules stabilize the protein-drug complexes by interacting with the ligands and binding pockets. Our results offer ideas that could be used in optimizing protein-drug interactions, by designing ligands that are capable of targeting localized water molecules in protein binding sites. The resulting free energy of ligand binding could benefit from the potential free energy gain accompanying the release of these water molecules. Furthermore, we have examined the theoretical background of the double-decoupling method and its connection to the molecular dynamics thermodynamic integration techniques. IS - 24 JF - J Am Chem Soc SN - 0002-7863 AD - Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0365, USA. dhamelbe@mccammon.ucsd.edu EP - 7689 TI - Standard free energy of releasing a localized water molecule from the binding pockets of proteins: double-decoupling method. VL - 126 SP - 7683 KW - water-ref AU - Hamelberg, D AU - McCammon, JA PY - 2004/06/23/ UR - http://dx.doi.org/10.1021/ja0377908 ER -