How AccuratelyDo Current Force Fields Predict Experimental Peptide Conformations?An Adiabatic Free Energy Dynamics Study.

The quality of classical biomolecularsimulations is inevitably limited by two problems: the accuracy ofthe force field used and the comprehensiveness of configuration spacesampling. In this work we tackle the sampling problem by carryingout driven adiabatic free energy dynamics to obtain converged freeenergy surfaces of dipeptides in the gas phase and in solution usingselected dihedral angles as collective variables. To calculate populationsof conformational macrostates observed in experiment, we introducea fuzzy clustering algorithm in collective-variable space, which delineatesmacrostates without prior definition of arbitrary boundaries. Withthis approach, we calculate the conformational preferences of smallpeptides with six biomolecular force fields chosen from among themost recent and widely used. We assess the accuracy of each forcefield against recently published Raman or IR–UV spectroscopymeasurements of conformer populations for the dipeptides in solutionor in the gas phase. [ABSTRACT FROM AUTHOR]