Molecular simulations free energy perturbations

Ding YB, Bernardo DN, Kroghjespersen K, Levy RM (1995) Solvation free-energies of small amides and amines from molecular-dynamics free-energy perturbation simulations using pairwise additive and many-body polarizable potentials. J Phys Chem 99(29) 11575—11583... 

Molecular dynamics free-energy perturbation simulations utilizing the empirical valence bond model have been used to study the catalytic action of -cyclodextrin in ester hydrolysis. Reaction routes for nucleophilic attack on m-f-butylphenyl acetate (225) by the secondary alkoxide ions 0(2) and 0(3) of cyclodextrin giving the R and S stereoisomers of ester tetrahedral intermediate were examined. Only the reaction path leading to the S isomer at 0(2) shows an activation barrier that is lower (by about 3kcal mol ) than the barrier for the corresponding reference reaction in water. The calculated rate acceleration was in excellent agreement with experimental data. ... 

Solvation Free Energies of Small Amides and Amines from Molecular Dynamics/Free Energy Perturbation Simulations Using Pairwise Additive and Many-Body Polarizable Potentials. 

Einally, we draw attention to several review articles in this area. In 1986 Lowdin 23 considered various aspects of the historical development of computational QC in view of the development of both conventional supercomputers and large-scale parallel computers. More recently, Weineri24 presented a discussion on the programming of parallel computers and their use in molecular dynamics simulations, free energy perturbation, and large scale ab initio calculations, as well as the use of very elaborate graphical display programs in chemistry research. We also note a review on the use of parallel processors in... 

A molecular dynamics free-energy perturbation simulation (121) comparing the phosphonamidate and phosphonate in solution and in the enzyme... 

Validation of the OPLS2.0 force field includes comparison to quantum mechanical energy profiles and experimental solvation free energies. For the latter, we performed explicit solvent molecular dynamics free energy perturbation simulations on a set of 239 diverse small molecules [80]. Compared with other popular force fields... 

P. Auffinger and G. Wipff,/. Chim. Phys., 88,2525 (1991). Quantitative Studies on Molecular Recognition Free Energy Perturbation Simulations on M c222 Cryptates in Water and in Methanol. 

T.P. Lybrand, Computer simulations of biomolecular systems using molecular dynamics and free energy perturbation methods, in Reviews in Computational Chemistry, Vol. 1, K.B. Lipkowitz, D.B. Boyd (Eds.), VCH, New York, 1990, pp. 295-320. 

Calculations of relative partition coefficients have been reported using the free energy perturbation method with the molecular dynamics and Monte Carlo simulation methods. For example, Essex, Reynolds and Richards calculated the difference in partition coefficients of methanol and ethanol partitioned between water and carbon tetrachloride with molecular dynamics sampling [Essex et al. 1989]. The results agreed remarkably well with experiment... 

In our simulations of histone modifying enzymes, the computational approaches centered on the pseudobond ab initio quantum mechanical/molecular mechanical (QM/MM) approach. This approach consists of three major components [20,26-29] a pseudobond method for the treatment of the QM/MM boundary across covalent bonds, an efficient iterative optimization procedure which allows for the use of the ab initio QM/MM method to determine the reaction paths with a realistic enzyme environment, and a free energy perturbation method to take account... 

Lu, N. Kofke, D. A., Accuracy of free-energy perturbation calculations in molecular simulation. I. Modeling, J. Chem. Phys. 2001,114, 7303-7312... 

In this chapter, we will examine in depth the characteristic errors of two free energy techniques and present improved methods based on a better understanding of their behavior. The two techniques examined are free energy perturbation (FEP) [2] and nonequilibrium work (NEW) based on Jarzynski s equality [3-6]. These techniques are discussed in Chaps. 2 and 5. The FEP method is one of the most popular approaches for computing free energy differences in molecular simulation see, e.g., [1, 7-10]. The recently developed NEW method, which is closely related to FEP, is gaining popularity in both simulation [11-18] and experimental applications [19-21],... 

Kofke, D.A., Cummings, P.T., Precision and accuracy of staged free-energy perturbation methods for computing the chemical potential by molecular simulation, Fluid Phase... 

Pan, Y. P. Daggett, V., Direct comparison of experimental and calculated folding free energies for hydrophobic deletion mutants of chymotrypsin inhibitor. 2 Free energy perturbation calculations using transition and denatured states from molecular dynamics simulations of unfolding, Biochemistry 2001,40, 2723-2731. 

Whilst this Chapter is primarily concerned with the methods of determining the free energies of tautomeric or ionisation equilibria via computer simulation of free energy differences, many of the issues raised relate also to the determination of other molecular properties upon which behaviour of the molecule within the body may depend, such as the redox potential or the partition coefficient.6 In the next section, we shall give a brief explanation of the methods used to calculate these free energy differences -namely the use of a thermodynamic cycle in conjunction with ab initio and free energy perturbation (FEP) methods. This enables an explicit representation of the solvent environment to be used. In depth descriptions of the various simulation protocols, or the accuracy limiting factors of the simulations and methods of validation, have not been included. These are... 

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