Free energy surface conformational

Y. Wang and K. Kuczera. Exploration of conformational free energy surface of helical Ala and Aibn peptides. J. Phys. Chem. B, 101 5205-5213, 1997. 

Y. Wang and K. Kuczera. Conformational free energy surface of the linear DPDPE peptide Cost of pre-organization for disulfide bond formation. J. Am. Chem. Soc., submitted, 1997. 

The function U fXj is called the PMF it was first introduced by Kirkwood to describe the structure of liquids [61]. It plays the role of a free energy surface for the solute. Notice that the dynamics of the solute on the free energy surface W(X) do not correspond to the true dynamics. Rather, an MD simulation on 1T(X) should be viewed as a method to sample conformational space and to obtain equilibrium, thermally averaged properties. 

Summary. We recently developed an all-atom free energy force field (PFFOl) for protein structure prediction with stochastic optimization methods. We demonstrated that PFFOl correctly predicts the native conformation of several proteins as the global optimum of the free energy surface. Here we review recent folding studies, which permitted the reproducible all-atom folding of the 20 amino-acid trp-cage protein, the 40-amino acid three-helix HIV accessory protein and the sixty amino acid bacterial ribosomal protein L20 with a variety of stochastic optimization methods. These results demonstrate that all-atom protein folding can be achieved with present day computational resources for proteins of moderate size. 

Figure 4.2 illustrates the parabolic free-energy surfaces as a function of reaction coordinate. In particular, three different kinetic regimes are shown in accordance with the classical Marcus theory. The reorganization energy, X, represents the change in free energy upon transformation of the equilibrium conformation of the reactants to the equilibrium conformation of the products when no electron is... 

We compute free energy surfaces in the (f,f ) space, 3/(Hc,HN) dipolar couplings and radial distribution functions (RDF) which show that (1) PM3 is incapable of reproducing the conformational distribution of alanine dipeptide (2) the peptide correction does not improve the results (3) the addition of the PDDG function to PM3 can noticeably improve the energetics and (4) none of the QM methods can reproduce the experiment better than the classical ff99SB force field. 

The free energy surfaces for AD at 300 K were obtained by calculating the (normalized) probability P of finding the AD in a conformation at a particular region in (, VQ-space from the REMD/MD trajectories, then converting this number to free... 

Natural proteins are able to fold to specific structures because, on average, native-like interactions between residues are more stable than non-native ones. The former are therefore more persistent and the polypeptide chain is able to find its lowest energy structure by a process of trial and error. Moreover, if the free energy surface or landscape has the right shape (see Fig. 13.1), only a minute fraction of all possible conformations is sampled by any given... 

Figure 1 Schematic representation of a potential energy surface with two minima. The larger width of the higher-energy minimum B (leading to greater flexibility compared with the narrower lower-energy minimum A) could result in a lower free energy for conformation B that fluctuates about the higher-energy minimum.

Grubmiiller [92] proposed a method that destabilises the initial conformation with an artificial potential, and renders transitions between substates separated by energy barriers higher than the thermal energy accessible on the simulation time scale. During the MD simulation, the shape of the potential free energy surface is estimated with an effective harmonic potential [93]. A flooding potential... 

Figure 19 Free energy surfaces for correct (R, top) and incorrect (W, bottom) incorporations by T7 DNA Polymerase. TSC, TS1, and TS2 subscripts refer to transition states for conformational change, 03 -Pa bond formation, and pyrophosphate departure, respectively. Wjsic and Wts2c refer to transition states for mismatched incorporation in a fully closed conformation. Adapted with permission from J. Florian M. F. Goodman A. Warshel, Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 6819-6824. Copyright 2005 National Academy of Sciences.

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