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Molecular Recognition and Ligand Association
Baron, R., J.A. McCammon
Molecular Basis of Calcium-sensitizing Mutations of the Human Cardiac Troponin C Regulatory Domain: A multi-scale simulation study
Kekenes-Huskey, P.M., S. Lindert, J.A. McCammon
Accelerated Molecular Dynamics: An efficient enhanced sampling method for biomolecular simulations
Pierce, L.C.T., W. Sinko, J.A. McCammon
On the Role of Dewetting Transitions in Host-Guest Binding Free Energy Calculations
Rogers, K., J.M. Ortiz-Sanchez, R. Baron, M. Fajer, C.A.F. de Oliveira, J.A. McCammon
Structural insight into the separate roles of IP4 and DAD in activation of histone deacetylase 3
Arrar, M., R. Turnham, L. Pierce, C.A.F. de Oliveira, J.A. McCammon
Allosteric Networks in Thrombin Distinguish Procoagulant vs. Anticoagulant Activities
Gasper,P., B. Fuglestad, E. Komives, P. Markwick, J.A. McCammon
Antibacterial drug leads targeting isoprenoid biosynthesis
Zhu, W., Y. Zhang, W. Sinko, M. Hensler, J. Olson, K.J. Molohon, S. Lindert, R. Cao, K. Li, K. Wang, Y. Wang, Y.L. Liu, A. Sankovsky, C.A.F. de Oliveira, D.A. Mitchell, V. Nizet, J.A. McCammon, E. Oldfield
w-REXAMD: A Hamiltonian replica exchange approach to improve free energy calculations for systems with kinetically-trapped conformations
Arrar, M., M. Fajer, W. Sinko, C. de Oliveira, J.A. McCammon
Solvent fluctuations in hydrophobic cavity-ligand binding kinetics
Setny, P., R. Baron, P. Kekenes-Huskey, J.A. McCammon, J. Dzubiella
Fluoroketone Inhibition of Ca++-Independent Phospholipase A2 through Binding Pocket Association Defined by Hydrogen/Deuterium Exchange and Molecular Dynamics.
Hsu, Y.H., D. Bucher, J. Cao, S. Li, S.W. Yang, G. Kokotos, V. Woods, J. McCammon, E. Dennis
The mechanism of inhibition of Group VIA Ca2+-independent phospholipase A2 (iPLA2) by fluoroketone (FK) ligands is examined using a combination of deuterium exchange mass spectrometry (DXMS) and molecular dynamics (MD). Models for iPLA2 were built by homology with the known structure of patatin and equilibrated by extensive MD simulations. Empty pockets were identified during the simulations and studied for their ability to accommodate FK inhibitors. Ligand docking techniques showed that the potent inhibitor 1,1,1,3-tetrafluoro-7-phenylheptan-2-one (PHFK) forms favorable interactions inside an active site pocket where it blocks the entrance of phospholipid substrates. The polar fluoroketone head group is stabilized by hydrogen bonds with residues Gly486, Gly487, and Ser519. The nonpolar aliphatic chain and aromatic group are stabilized by hydrophobic contacts with Met544, Val548, Phe549, Leu560, and Ala640. The binding mode is supported by DXMS experiments showing an important decrease of deuteration in the contact regions in the presence of the inhibitor. The discovery of the precise binding mode of FK ligands to the iPLA2sub> should greatly improve our ability to design new inhibitors with higher potency and selectivity.