@article {19368,
	title = {Structural and dynamic determinants of ligand binding and regulation of cyclin-dependent kinase 5 by pathological activator p25 and inhibitory peptide CIP.},
	journal = {Journal of molecular biology},
	volume = {401},
	year = {2010},
	month = {2010 Aug 20},
	pages = {478-92},
	abstract = {The crystal structure of the cdk5/p25 complex has provided information on possible molecular mechanisms of the ligand binding, specificity, and regulation of the kinase. Comparative molecular dynamics simulations are reported here for physiological conditions. This study provides new insight on the mechanisms that modulate such processes, which may be exploited to control pathological activation by p25. The structural changes observed in the kinase are stabilized by a network of interactions involving highly conserved residues within the cyclin-dependent kinase (cdk) family. Collective motions of the proteins (cdk5, p25, and CIP) and their complexes are identified by principal component analysis, revealing two conformational states of the activation loop upon p25 complexation, which are absent in the uncomplexed kinase and not apparent from the crystal. Simulations of the uncomplexed inhibitor CIP show structural rearrangements and increased flexibility of the interfacial loop containing the critical residue E240, which becomes fully hydrated and available for interactions with one of several positively charged residues in the kinase. These changes provide a rationale for the observed high affinity and enhanced inhibitory action of CIP when compared to either p25 or the physiological activators of cdk5.},
	keywords = {Crystallography, X-Ray, Cyclin-Dependent Kinase 5, Cyclin-Dependent Kinase Inhibitor Proteins, HUMANS, Ligands, molecular dynamics simulation, Nerve Tissue Proteins, Principal component analysis, Protein Binding, Protein Conformation},
	issn = {1089-8638},
	doi = {10.1016/j.jmb.2010.06.040},
	author = {Cardone, Antonio and Hassan, S A and Albers,R.W. and Sriram,R.D. and Pant,H.C.}
}
@article {18704,
	title = {Impact of Cl- and Na+ ions on simulated structure and dynamics of βARK1 PH domain},
	journal = {Proteins: Structure, Function, and Bioinformatics},
	volume = {35},
	year = {1999},
	month = {1999///},
	pages = {206 - 217},
	abstract = {A nonzero net charge of proteins at pH 7 is usually compensated by the addition of charge-balancing counter ions during molecular dynamics simulation, which reduces electrostatic interactions. For highly charged proteins, like the βARK1 PH domain used here, it seems reasonable to also add explicit salt ions. To assess the impact of explicit salt ions, two molecular dynamics simulations of solvated βARK1 PH domain have been carried out with different numbers of Cl- and Na+ ions, based on the Cornell et al. force field and the Ewald summation, which was used in the treatment of long-range electrostatic interactions. Initial positions of ions were obtained from the AMBER CION program. Increasing the number of ions alters the average structure in loop regions, as well as the fluctuation amplitudes of dihedral angles. We found unnaturally strong interactions between side chains in the absence of salt ions. The presence of salt ions reduces these electrostatic interactions. The time needed for the equilibration of the ionic environment around the protein, after initial placement of ions close to oppositely charged side chains, is in the nanosecond time range, which can be shortened by using a higher ionic strength. Our results also suggest selecting those methods that do not place the ions initially close to the protein surface. Proteins 1999;35:206{\textendash}217. {\textcopyright} 1999 Wiley-Liss, Inc.},
	keywords = {counter ions, electrostatic interaction, equilibration, GRK2 PH domain, hydrogen bonds, ionic solvent, ionic strength, molecular dynamics simulation, Proteins},
	isbn = {1097-0134},
	doi = {10.1002/(SICI)1097-0134(19990501)35:2<206::AID-PROT7>3.0.CO;2-A},
	url = {http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0134(19990501)35:2<206::AID-PROT7>3.0.CO;2-A/abstract},
	author = {Pfeiffer,Stefania and Fushman, David and Cowburn,David}
}
