Free energy calculations methods

We assume that the unbinding reaction takes place on a time scale long ( ompared to the relaxation times of all other degrees of freedom of the system, so that the friction coefficient can be considered independent of time. This condition is difficult to satisfy on the time scales achievable in MD simulations. It is, however, the most favorable case for the reconstruction of energy landscapes without the assumption of thermodynamic reversibility, which is central in the majority of established methods for calculating free energies from simulations (McCammon and Harvey, 1987 Elber, 1996) (for applications and discussion of free energy calculation methods see also the chapters by Helms and McCammon, Hermans et al., and Mark et al. in this volume). 

Radmer, R.. 1., Kollman, P. A. Approximate free energy calculation methods and structiire based ligand design. J. Comp. Aid. Mol. Desgn (in press)... 

Rodriguez-Gomez, D. Darve, E. Pohorille, A., Assessing the efficiency of free energy calculation methods, J. Chem. Phys. 2004,120, 3563-3578... 

Oberhofer, H. Dellago, C. Geissler, P. L., Biased sampling of nonequilibrium trajectories. Can fast switching simulations outperform conventional free energy calculation methods, J. Phys. Chem. B 2005,109, 6902-6915... 

Radmer, R.J., Kollman, P.A., Free energy calculation methods a theoretical and empirical comparison of numerical errors and a new method for qualitative estimates of free energy changes, J. Comput. Chem. 1997,18, 902-919... 

Pearlman, D.A., Govinda, R., Free energy calculations methods and applications. In Encyclopedia of Computational Chemistry, Schleyer, P., Ed. Wiley Chichester, 1998... 

Finally, in Sect. 7.6, we have discussed how various free energy calculation methods can be applied to determine free energies of ensembles of pathways rather than ensembles of trajectories. In the transition path sampling framework such path free energies are related to the time correlation function from which rate constants can be extracted. Thus, free energy methods can be used to study the kinetics of rare transitions between stable states such as chemical reactions, phase transitions of condensed materials or biomolecular isomerizations. 

Radmer, R J. Kollman, P.A., The application of three approximate free energy calculations methods to structure based ligand design trypsin and its complex with inhibitors., J. Comput. Aided Mol. Des. 1998,12, 215-227... 

D. A. Pearlman and B. G. Rao, Free energy calculations Methods and applications,... 

Free Energy Calculations Methods for Estimating Ligand Binding Affinities... 

The incorporation of the generalized Bom model into free energy calculation methods using FEP/TI and A-dynamics was carried out by Banba and Brooks.81 They define the electrostatic solvation energy for the hybrid system as follows... 

R. J. Radmer and P. A. Kollman, Free energy calculation methods A theoretical and... 

D. Rodriguez-Gomez, E. Darve, and A. Pohorille (2004) Assessing the efficiency of free energy calculation methods J. Chem,. Phys. 120, p. 3563 L. Rosso, P. Minary, Z. Zhu, and M. Tuckerman (2002) On the use of the adiabatic molecular dynamics technique in the calculation of free energy profiles. J. Chem. Phys. 116, pp. 4389-4402... 

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