Computational Drug Discovery and Design

VrðÞ∗¼V 0 ðÞþr ΔVboostðÞr

Depending on the type of the boost potential (ΔVboost(r)), we

distinguish three methods of aMD.

1. Boosting only the dihedral potential energy byΔVd(r):

ΔVdðÞ¼r

ðÞEthrdVdðÞr^2

ðÞαDþEthrdVdðÞr

whereVd(r),Ethrd, andαDare respectively the dihedral energy,

the dihedral energy threshold, and the boost factor for the dihedral

energy.

In this case, the boost is applied whenVd(r)<Ethrd

2. Boosting the total potential energy byΔVT(r):

ΔVTðÞ¼r

ðÞEthrpVrðÞ^2

ðÞαPþEthrpVrðÞ

whereV(r)¼V 0 (r)+ΔVd(r) andEthrp,αPare respectively the

total potential energy threshold and the boost factor for the total

potential energy.

3. The dual boost aMD byΔVTd(r)[35], in which the boost is
   added on the total potential energy in addition of an extra
   boost on the dihedral energy:

ΔVTdðÞ¼r ΔVTðÞþr ΔVdðÞr

In these last two cases (ΔVT(r) and ΔVTd(r)), the boost is

applied whenV(r)<Ethrp.

In our simulations, we use the dual boost aMD to study the

improvement of the sampling of the conformational space of the

protein structure compared to the cMD (seeNote 7).

3.4.2 Parametrization
of aMD Simulation

The parameters that have to be specified by the user and that

directly impact the acceleration of the molecular dynamics simula-

tion are: the total potential energy threshold (Ethrp), the dihedral

energy threshold (Ethrd), the boost factorsαPandαD. Note that

αPandαDare inversely proportional to the strength of the applied

acceleration. The bigger isEthr(EthrporEthrd), the greater is the

region of the potential energy surface affected by the boost,

whereas the smaller isα(αPorαD), the more flattened is the energy

barrier, which will be easier to cross (Fig.1)(seeNote 8).

As it was suggested in previous aMD studies [36, 37], it is

recommended to calculate these parameters from the estimated

average of total potential and dihedral energies (hEp(tot)iand

Enhanced Molecular Dynamics 411