Author : Huan Zhan
Publisher :
ISBN 13 : 9781303088711
Total Pages : 198 pages
Book Rating : 4.0/5 (887 download)
Book Synopsis Enhancements to Implicit Solvent Modeling of Peptides in Water and in Lipid Bilayers by : Huan Zhan
Download or read book Enhancements to Implicit Solvent Modeling of Peptides in Water and in Lipid Bilayers written by Huan Zhan and published by . This book was released on 2013 with total page 198 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years implicit solvation models have been increasingly used in molecular dynamics (MD) simulations of proteins/peptides due to their computational efficiency. While these models can account for electrostatic interactions and hydrophobic effect of proteins/peptides in both water and lipid membranes, other properties of the solvent, such as the local dielectric screening effect at the binding sites of metalloproteins, the membrane dipole potential, and the membrane lateral pressure, have not yet been included. In this work, first the effective energy function (EEF1) is extended to simulate metalloproteins by neutralizing ligand carboxylates based on their exposure to solvent water. The new model is then applied to MD simulation of calcium-binding proteins calbindin d9k, calmodulin, troponin C, and parvalbumin. Although structures consistent with experiments are obtained, the model is limited by the fact that the selection of charges for carboxylates is arbitrary, and that the charges cannot be modified as the protein structure changes during the simulation. Second the implicit membrane mode (IMM1) is extended to include the membrane dipole potential, and the new model is applied to MD simulation of the helical peptides alamethicin, WALP23, influenza hemagglutinin fusion peptide, HIV fusion peptide, magainin, and the pre-sequence of cytochrome c oxidase subunit IV (p25). The results show that the orientation of the peptides in the membrane can be influenced by the dipole potential. In general peptides that tend to insert the N-terminus in the membrane and/or have positively charged side chains will lose binding affinity upon increase of the dipole potential. Finally, IMM1 is extended to include lateral pressure effects and tested by MD simulation of the peptides alamethicin, melittin, cyclotide kalata B1, 18A, and KKpL15. The simulations of alamethicin binding to pure DOPC bilayer show that increase in the peptide/lipid molar ratio favors the transmembrane orientation, which is explained by the difference in the cross-sectional area of the two orientations. The simulations of all peptides binding to mixed DOPC/DOPE bilayers show that the binding energy can increase, decrease, or not change as the molar fraction of DOPE increases, which is explained by the difference in the binding location of the peptides.
