Ahlam N. Al-Rawi

Structural characterization of two pore-forming peptides: Consequences of introducing a C-terminal tryptophan

Synthetic channel‐forming peptides that can restore chloride conductance across epithelial membranes could provide a novel treatment of channelopathies such as cystic fibrosis. Among a series of 22‐residue peptides derived from the second transmembrane segment of the glycine receptor α1‐subunit (M2GlyR), p22‐S22W (KKKKP ARVGL GITTV LTMTT QW) is particularly promising with robust membrane insertion and assembly. The concentration to reach one‐half maximal short circuit current is reduced to 45 ± 6 μM from that of 210 ± 70 μM of peptide p22 (KKKKP ARVGL GITTV LTMTT QS). However, this is accompanied with nearly 50% reduction in conductance. Toward obtaining a molecular level understanding of the channel activities, we combine information from solution NMR, existing biophysical data, and molecular modeling to construct atomistic models of the putative pentameric channels of p22 and p22‐S22W. Simulations in membrane bilayers demonstrate that these structural models, even though highly flexible, are stable and remain adequately open for ion conductance. The membrane‐anchoring tryptophan residues not only rigidify the whole channel, suggesting increased stability, but also lead to global changes in the pore profile. Specifically, the p22‐S22W pore has a smaller opening on average, consistent with lower measured conductance. Direct observation of several incidences of chloride transport suggests several qualitative features of how these channels might selectively conduct anions. The current study thus helps to rationalize the functional consequences of introducing a single C‐terminal tryptophan. Availability of these structural models also paves the way for future work to rationally modify and improve M2GlyR‐derived peptides toward potential peptide‐based channel replacement therapy. Proteins 2010.

Theoretical studies of the surface phonon linewidth

A brief review of two theoretical methods for calculating the linewidth of surface phonons is presented with specific application to the low-Miller-index surfaces of Ag, Cu, and Al. In the quasi-analytic method, linewidths are calculated by treating the cubic term of a reliable interatomic potential in first-order, time-dependent perturbation theory. In molecular dynamics?(MD) simulations, linewidths are obtained from appropriate correlation functions and include the fully anharmonic contribution of the interaction potential. Surface relaxations and phonon frequencies calculated in the harmonic approximation, using selected many-body interatomic potentials, are found to be in good agreement with results from experimental data and ab initio calculations. At 300?K, the surface phonon linewidths range approximately between?1 and 0.1?THz, and are found to be in reasonable agreement with the values deduced from experiments. Some disagreement is found between results from perturbative methods and MD simulations. For the low-Miller-index surfaces of Ni, available results from MD simulations also summarized.

Theoretical study of the structure and vibrational dynamics of Cu3Au(511)

We have studied the structure and vibrational dynamics of Cu3Au(511) using embedded atom method potentials. The relaxation pattern of this surface shows a buckling in all Au-rich chains of about 0.14 A, which is similar to that found in Cu3Au(100). The relaxation pattern of this surface is qualitatively similar to that of Cu(511), but is more pronounced in Cu3Au(511) and extends deep into the bulk. Our calculations show that the local vibrational properties of this vicinal surface is sensitive to the local atomic environment. Surface Au atoms are responsible for a large softening of the force field at the surface, yielding a substantial shift toward low frequencies of the vibrational densities of states associated with Au surface atoms. As a consequence, the excess local free energy of the Au atoms are about 43 meV/atom at 663 K.

Paths, Barriers, and Prefactors for Adatom Descent from Ag Clusters on Ag(111)

We have calculated the energetics and the dynamics for the diffusion of Ag adatoms which land on top of small two-dimensional Ag clusters on Ag(111), using realistic many-body interaction potentials. Purely energetic considerations of the descent of the adatoms from the islands show exchange mechanism to dominate over hopping and the process to favor the formation of 100-microfacetted steps (A-type) over the 111-microfacetted ones (B-type). Accompanying molecular dynamics simulations validate these findings at low temperatures, but show a reversal in the trend above room temperature making the formation of B-type step more probable. Calculations of the diffusion coefficient confirm that the pre-exponential factor for the processes leading to the formation of the A and B type steps are significantly different.