Premium
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
Author(s) -
Daura Xavier,
Oliva Baldomero,
Querol Enrique,
Avilés Francesc X.,
Tapia Orlando
Publication year - 1996
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(199605)25:1<89::aid-prot7>3.0.co;2-f
Subject(s) - sensitivity (control systems) , force field (fiction) , carboxypeptidase , water model , test (biology) , field (mathematics) , chemistry , computer science , biochemistry , molecular dynamics , mathematics , computational chemistry , engineering , biology , artificial intelligence , botany , electronic engineering , pure mathematics , enzyme
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. © 1996 Wiley‐Liss, Inc.