Improving the GROMOS 53A6 force field Using NMR data.

MARCOS ARIEL VILLARREAL; GUILLERMO MONTICH; EZEQUIEL LEIVA

Rosario

Congreso; XXXV Reunión anual de la Sociedad Argentina de Biofísica; 2006

Sociedad Argentina de Biofísica

Recently, the GROMOS force field has been parametrized to reproduce free enthalpies of hydration of aminoacids analogs. Despite this advance, the parameters that govern the conformational preferences of the protein backbone remains largely unchanged since the early versions of the force field. An analysis of the ramachandran plots of peptides and proteins calculated from simulations in solution showed several deficiencies and artifacts in the GROMOS parameters set 53A6, which in this work we proposed to correct. Our approach to improve the conformational description of the peptide backbone is based on the reproduction of experimentally determined 3J(HN,Hƒ¿) NMR couplings, which are linked to the distribution of the Phi backbone angle. By changing key 1-4 Lennard-Jones and torsional parameters we were able to reproduce the couplings 3J(HN,Hƒ¿) to within 0.2 Hz. Comparison with other commonly used force fields, like AMBER and OPLS, showed that the parametrization developed have a better performance when calculating the couplings. This new improvement in the GROMOS force field together with its already established ability to describe the hydration of aminoacids, makes it a valuable tool to study not only the folded state of proteins but also the unfolded state, were 3J(HN,Hƒ¿) coupling are extensively used to obtain information of this elusive state.