Pbp3 3.1.0 free#
We present an adaptation of a nonlinear dimensionality reduction technique known as the diffusion map that extends its applicability to biased umbrella sampling simulation trajectories in which restraining potentials are employed to drive the system into high free energy regions and improve sampling of phase space. For molecular systems exhibiting free energy barriers exceeding a few kBT, inadequate sampling of the barrier regions between stable or metastable basins can lead to a poor global characterization of the free energy landscape. Nonlinear dimensionality reduction techniques can be applied to molecular simulation trajectories to systematically extract a small number of variables with which to parametrize the important dynamical motions of the system. Integrating diffusion maps with umbrella sampling: Application to alanine dipeptideįerguson, Andrew L. In αR, ethanol interacts with both carbonyl groups. From the analysis of solvent density maps it is concluded that, in the water-ethanol mixture, ethanol molecules are more likely found around the alanine side chain and the carbonyl group, but while in PPII ethanol molecules interact mainly with the carbonyl group of the N-terminal end, in C5 the interaction is with the carbonyl group of the C-terminal end. Remarkably, this fact does not affect the differential conformational stability that is controlled by long-range interactions. Our results point to the presence of preferential solvation in this system, the composition of the first solvation shell in the binary mixture being dominated by water molecules. The addition of ethanol increases the stability of the PPII conformer.
Internal energy favors the formation of PPII, whereas, on the contrary, solute-solvent interaction is favorable to αR, so any factor that decreases the solute-solvent interaction free energy will increase the PPII population.
The final in solution αR-PPII free energy difference is determined from the interplay between the internal energy of the dipeptide and the solute-solvent interaction free energy. In polar solution, only αR and PPII conformers contribute in an appreciable way to the conformational equilibrium. The AD molecule was described at the MP2/aug-cc-pVDZ level. Taking as a model system the alanine dipeptide (AD) we perform a QM/MM study in water, ethanol, and a 40-60% in volume water-ethanol mixture. However, the mechanism underlying this effect is not clear. Conformational Changes of the Alanine Dipeptide in Water-Ethanol Binary Mixtures.Īlmeida, Glauco G Cordeiro, João M M MartÃn, M Elena Aguilar, Manuel AĮxperimental work developed in the last years has evidenced the capacity of alcohols and polyalcohols to modify the energy landscape of peptides and proteins.