Improving macromolecular electrostatics calculations

Electrostatic interactions play a key role in many aspects of protein engin eering, Consequently, much effort has been put into the design of software for calculating electrostatic fields around macromolecules. We show that op timization of hydrogen bonding networks can improve both the results of pK( a) calculations and the results of electrostatic calculations performed by commonly used programs such as DelPhi, Further optimization can often be ac hieved by flipping the side chains of asparagine, histidine and glutamine a round their chi 2, chi 2 and chi 3 torsion angles, respectively, when this improves the local hydrogen bonding network. These optimizations are applie d to some well characterized proteins: BPTI, hen egg white lysozyme and sup eroxide dismutase, A search for flipped residues in the PDB revealed that s ignificant improvements in electrostatic calculations in or near the active site of enzymes can be expected for about one quarter of all enzymes in th e PDB.