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Hydration Free Energies (hydration + free_energy)
Selected Abstracts,-Dynamics free energy simulation methodsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 11 2009Jennifer L. Knight Abstract Free energy calculations are fundamental to obtaining accurate theoretical estimates of many important biological phenomena including hydration energies, protein-ligand binding affinities and energetics of conformational changes. Unlike traditional free energy perturbation and thermodynamic integration methods, ,-dynamics treats the conventional "," as a dynamic variable in free energy simulations and simultaneously evaluates thermodynamic properties for multiple states in a single simulation. In the present article, we provide an overview of the theory of ,-dynamics, including the use of biasing and restraining potentials to facilitate conformational sampling. We review how ,-dynamics has been used to rapidly and reliably compute relative hydration free energies and binding affinities for series of ligands, to accurately identify crystallographically observed binding modes starting from incorrect orientations, and to model the effects of mutations upon protein stability. Finally, we suggest how ,-dynamics may be extended to facilitate modeling efforts in structure-based drug design. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009 [source] Accuracy of free energies of hydration using CM1 and CM3 atomic chargesJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 11 2004Blagovi, Marina Udier Abstract Absolute free energies of hydration (,Ghyd) have been computed for 25 diverse organic molecules using partial atomic charges derived from AM1 and PM3 wave functions via the CM1 and CM3 procedures of Cramer, Truhlar, and coworkers. Comparisons are made with results using charges fit to the electrostatic potential surface (EPS) from ab initio 6-31G* wave functions and from the OPLS-AA force field. OPLS Lennard,Jones parameters for the organic molecules were used together with the TIP4P water model in Monte Carlo simulations with free energy perturbation theory. Absolute free energies of hydration were computed for OPLS united-atom and all-atom methane by annihilating the solutes in water and in the gas phase, and absolute ,Ghyd values for all other molecules were computed via transformation to one of these references. Optimal charge scaling factors were determined by minimizing the unsigned average error between experimental and calculated hydration free energies. The PM3-based charge models do not lead to lower average errors than obtained with the EPS charges for the subset of 13 molecules in the original study. However, improvement is obtained by scaling the CM1A partial charges by 1.14 and the CM3A charges by 1.15, which leads to average errors of 1.0 and 1.1 kcal/mol for the full set of 25 molecules. The scaled CM1A charges also yield the best results for the hydration of amides including the E/Z free-energy difference for N -methylacetamide in water. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1322,1332, 2004 [source] Rational determination of charge distributions for free energy calculationsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 4 2003Christophe Chipot Abstract Point charges derived from RHF/6-31G* electrostatic potentials are attractive because they tend to exaggerate the polarity of solvated molecules, thereby compensating in an average fashion missing induction effects. In the context of free energy calculations, wherein the molecule is transferred from a polar environment to a nonpolar one, we propose a more rational approach based on a self-consistent reaction field computation at a higher level of theory, supplemented by an estimation of the corresponding distortion energy to account for the change of polarity of the surroundings. Application of this method to the test cases acetamide, acetic acid, methyl acetate and phenol, using multinanosecond molecular dynamics/"umbrella sampling" simulations, yields consistent hydration free energies in reasonably good agreement with experiment. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 409,415, 2003 [source] Contribution of the trifluoroacetyl group in the thermodynamics of antigen,antibody bindingJOURNAL OF MOLECULAR RECOGNITION, Issue 3 2010Masayuki Oda Abstract We analyzed the binding of the 7C8 antibody to the chloramphenicol phosphonate antigens,one containing a trifluoroacetyl group (CP-F) and the other containing an acetyl group (CP-H),by using isothermal titration calorimetry (ITC). The thermodynamic difference due to the substitution of F by H was evaluated using free energy calculations based on molecular dynamics (MD) simulations. We have previously shown that another antibody, namely, 6D9, binds more weakly to CP-H than to CP-F, mainly due to the different hydration free energies of the dissociated state and not due to the unfavorable hydrophobic interactions with the antibody in the bound state. Unlike in the binding of the trifluoroacetyl group with 6D9, in its binding with 7C8, it is exposed to the solvent, as seen in the crystal structure of the complex of 7C8 with CP-F. The thermodynamic analysis performed in this study showed that the binding affinity of 7C8 for CP-H is similar to that for CP-F, but this binding to CP-H is accompanied with less favorable enthalpy and more favorable entropy changes. The free energy calculations indicated that, upon the substitution of F by H, enthalpy and entropy changes in the associated and dissociated states were decreased, but the magnitude of enthalpy and entropy changes in the dissociated state was larger than that in the associated state. The differences in binding free energy, enthalpy, and entropy changes determined by the free energy calculations for the substitution of F by H are in good agreement with the experimental results. Copyright © 2009 John Wiley & Sons, Ltd. [source] Application of the multiensemble sampling to the hydration free energyJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 10 2001Kyu-Kwang Han Abstract We demonstrate the feasibility of using multiensemble sampling method (MESM) to determine the free energy difference between two far states for which the configurational distributions do not overlap at all. The MESM is a recently developed non-Boltzmann sampling technique. The free energy of charging a sodium ion in water is accurately calculated in a single simulation, introducing nine intermediate ionic states. This is due to the ability of the method to explore the relevant parts of configuration space equally for every state, and this ability comes from the universality of weighting function W and the simplicity in adjusting its parameters. Detailed procedures of adjusting the parameters are presented. The comparison with a free energy perturbation method (FEPM) shows that the MESM is more reliable and efficient. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1004,1009, 2001 [source] | ||||||||||