Peptoids are N-substituted glycine oligomers featuring a large structural and functional diversity. Oligomer-based libraries of these biomimetics have been used in a wide range of biological applications, such as map epitopes for antibody binding, to discern ribonucleotide sequences with specific binding or catalytic activity, and to provide initial leads in receptor-based assays. The main advantages of peptoids, over peptides, are their thermal and environmental stability, proteolysis resistance and simple synthesis. These advantages are mainly due to the lack of a chiral center and the lack of inter- and intrachain hydrogen bonding in the peptoid backbone. In addtition, peptoids display an increased flexibility resulting from their ability to isomerize amide bonds at room temperature. Therefore, force field parameters for proteins have been shown inadequate to describe the dynamical behavior of peptoid amide bonds. To overcome this limitation, we have derived a peptoid-specific set of parameters for the GROMOS force field that are capable to describe the cis/trans isomerism arising from n-&gt;π* transitions as well as the conformational preferences for a number of peptoid model compounds in different solvents. They include a new charge set and van de Waals coefficients for aromatic carbon atoms and a modified amide bond torsional parameter. The results from molecular dynamics simulations show a converged sampling within a few hundreds nanoseconds at room temperature. Nevertheless, compared to peptides, longer timescale simulations are required due to the extra degree of freedom along the amide bond. Simulations of monomers and oligomers are validated against NMR and X-ray crystallography data. Insights into the propensity of secondary structure in peptoids as a function of their sequence is also discussed. This work is supported by CNPq, CAPES, FACEPE and NIH. Partial computational resources were provided by the Swiss National Supercomputing Centre (CSCS).

Extension and validation of the GROMOS force field for the simulation of peptoids

251st National Meeting (2016)

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