Table 2Description of various molecular dynamics methods: characteristics, limits and applications
Linear timedependance?Reactioncoordinatedependance?Methods to biasthe systemCharacteristicsLimitsExamples of applicationcMDYesNoNo bias introducedNeed long simulation time to cross highenergy barrierlConformational sampling
lStudy of Binding/unbinding process
lCharacterization of open/close state of protein stateand opening/closingchannelsScaled MD&aMDModificationof potentialenergysurfacelSampling is not directed
lAdd of a modified potential energyto the original potential energyLong simulations often lead to greaterstatistical errorslConformational sampling
lCharacterization of open/close state of protein stateand opening/closingchannels
lEstimation of free energyUS & SMDYeslSampling along a geometricalreaction coordinate (distance,angle, etc)
lAdd an harmonic potential energyto the original potential energylChoice of reaction coordinate
lBias parametrization is very systemdependentlConformational sampling
lStudy of Binding/unbinding process
lStudy of unfolding/foldingprocess
lCharacterization of open/close state of protein andopening/closing channels
lEstimation of free energy ofstudied eventsTMDlSampling along the RMSD asreaction coordinate
lAdd an harmonic potential energyto the original potential energyMTDlSampling along collective variablesdefined as one or a combination ofgeometrical reaction coordinate
lAdd a Gaussian potential energy tothe original potential energyChoice of CVsREMDNoNoMulticopysearchingandsamplinglSampling is not directed
lSeveral variants of REMD: T-REMD, R-REMD, H-REMD, M-REMD etc.lNo time evolution of structuralevents
lNumber of replicas dependent onsize systemConformational samplingSATemperaturescalinglSampling is not directed
lSampling equivalent to the unbiasedsystemNo time evolution of structural events410 Sonia Ziada et al.