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Protein Engineering, Vol. 12, No. 8, 657-662, August 1999
© 1999 Oxford University Press

Improving macromolecular electrostatics calculations

J. E. Nielsen1, K. V. Andersen2, B. Honig3, R. W. W. Hooft4, G. Klebe5, G. Vriend1,6 and R. C. Wade1

1 European Molecular Biology Laboratory, 69117 Heidelberg, Germany, 2 Novo Nordisk A/S, 2880 Bagsværd, Denmark, 3 Columbia University,New York, NY 10032, USA, 4 Nonius BV, Delft, The Netherlands and 5 University of Marburg, 35032 Marburg, Germany

Electrostatic interactions play a key role in many aspects of protein engineering. Consequently, much effort has been put into the design of software for calculating electrostatic fields around macromolecules. We show that optimization of hydrogen bonding networks can improve both the results of pKa calculations and the results of electrostatic calculations performed by commonly used programs such as DelPhi. Further optimization can often be achieved by flipping the side chains of asparagine, histidine and glutamine around their {chi}2, {chi}2 and {chi}3 torsion angles, respectively, when this improves the local hydrogen bonding network. These optimizations are applied to some well characterized proteins: BPTI, hen egg white lysozyme and superoxide dismutase. A search for flipped residues in the PDB revealed that significant improvements in electrostatic calculations in or near the active site of enzymes can be expected for about one quarter of all enzymes in the PDB.

Keywords: electrostatics/hydrogen bond network/pKa calculations/structure correction

6 To whom correspondence should be addressed.E-mail: vriend{at}embl-heidelberg.de


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