Biased or Restrained MD

The perturbation applied to the potential energy function has the harmonic form given in Eq. [6], where W is the biasing force applied on the 

By applying the same biasing potential, as in Eq. [6], depending on whether the simulation moves toward satisfaction of the target O-values or not, can produce conformations with the fraction of native contacts for each residue in correspondence with the O-values. 

O-values were used in individual sets of BMD simulations to generate putative conformational ensembles for each of the transition states. The relationship between SASA and the P values was in turn used to validate the conformations predicted through the MD simulations and selection of the TSEs. A range of elevated temperatures was also used in conjunction with the biasing potential to expand the sampling of the conformational space coincident with the O-values. 

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