On the sensitivity of MD trajectories to changes in water-protein interaction parameters: The potato carboxypeptidase inhibitor in water as a test case for the GROMOS force field

Xavier Daura, Baldomero Oliva, Enrique Querol, Francesc X. Avilés, Orlando Tapia

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39 Citations (Scopus)

Abstract

A critical evaluation is presented of the sensitivity of the results of molecular dynamics simulations of proteins to changes in the parameters describing water-protein and protein-protein van der Waals interactions in the GROMOS force field. The origin of the van der Waals and electrostatic parameters of the GROMOS standard force field is reviewed, and possible weaknesses are discussed. Four alternate sets of van der Waals parameters for the oxygen types of the GROMOS force field that have been suggested by different authors are then tested against the original force field. Six 500 ps molecular dynamics simulations of the potato carboxypeptidase inhibitor (PCI) in solution using the different parameter sets are analyzed and the results compared with the available X-ray and NMR data. It is shown that the behavior of the molecular system is very sensitive to changes in the van der Waals parameters of the oxygens, especially when affecting the interactions between water and aliphatic or aromatic groups. It is also shown that correction of just the repulsive van der Waals parameter of the water oxygen for its interactions with nonpolar groups is sufficient to correct the main deficiency of the original GROMOS parameter set. Nevertheless, the present study suggests that further refinement of the current parameters is still needed for a proper representation of nonbonded interactions.
Original languageEnglish
Pages (from-to)89-103
JournalProteins: Structure, Function and Genetics
Volume25
Issue number1
DOIs
Publication statusPublished - 4 Jun 1996

Keywords

  • computer simulation
  • force-field analysis
  • molecular dynamics of proteins
  • van der Waals interactions
  • water solvation properties

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