Biomedical subjects

Joanna Berdys-Kochanska

Publications and source records attributed to Joanna Berdys-Kochanska.

5 recordsLinked to original sources

PubMed2006

Simulating electron transfer attachment to a positively charged model peptide.

Ab initio electronic structure methods, including stabilization method tools for handling electronically metastable states, are used to treat a model system designed to probe the electron-transfer event characterizing electron-transfer dissociation (ETD) mass spectroscopic studies of peptides. The model system consists of a cation H(3)C-(C=O)NH-CH(2)-CH(2)-NH(3)(+), containing a protonated amine site and an amide site, that undergoes collisions with a CH(3)(-) anion. Cross-sections for electron transfer from CH(3)(-) to the protonated amine site are shown to exceed those for transfer to the Coulomb-stabilized amide site by 2 orders of magnitude. Moreover, it is shown that the fates of the amine-attached and amide-attached species are similar in that both eventually lead to the same carbon-centered radical species H(3)C-((*)C-OH)NH-CH(2)-CH(2)-NH(2), although the reaction pathways by which the two species produce this radical are somewhat different. The implications for understanding peptide fragmentation patterns under ETD conditions are also discussed in light of this work's findings.

Amides↗

PubMed2005

Electron attachment step in electron capture dissociation (ECD) and electron transfer dissociation (ETD).

We have made use of classical dynamics trajectory simultions and ab initio electronic structure calculations to estimate the cross sections with which electrons are attached (in electron capture dissociation (ECD)) or transferred (in electron transfer dissociation (ETD)) to a model system that contained both an S-S bond that is cleaved and a -NH(3)(+) positively charged site. We used a Landau-Zener-Stueckelberg curve-crossing approximation to estimate the ETD rates for electron transfer from a CH(3)(-) anion to the -NH(3)(+) Rydberg orbital or the S-S sigma* orbital. We draw conclusions about ECD from our ETD results and from known experimental electron-attachment cross sections for cations and sigma-bonds. We predict the cross section for ETD at the positive site of our model compound to be an order of magnitude larger than that for transfer to the Coulomb-stabilized S-S bond site. We also predict that, in ECD, the cross section for electron capture at the positive site will be up to 3 orders of magnitude larger than that for capture at the S-S bond site. These results seem to suggest that attachment to such positive sites should dominate in producing S-S bond cleavage in our compound. However, we also note that cleavage induced by capture at the positive site will be diminished by an amount that is related to the distance from the positive site to the S-S bond. This dimunition can render cleavage through Coulomb-assisted S-S sigma* attachment competitive for our model compound. Implications for ECD and ETD of peptides and proteins in which SS or N-C(alpha) bonds are cleaved are also discussed, and we explain that such events are most likely susceptible to Coulomb-assisted attachment, because the S-S sigma* and C=O pi* orbitals are the lowest-lying antibonding orbitals in most peptides and proteins.

Algorithms↗

PubMed2005

A theoretical model for indirect dissociative electron attachment.

In this paper, we describe a computational model that allows us to avoid having to perform a very large number of tedious calculations on electronically metastable anions when studying indirect DEA processes. By indirect, we mean that the electron attaches to an orbital in one region of the molecule but a bond is subsequently broken in another region. For such events, one must describe the coupling between two diabatic anion states, corresponding to the occupation of orbitals in the two regions of the molecule, to achieve a correct description. We introduce a simple 2 x 2 matrix model as well as physically reasonable and computationally efficient approximations to the diabatic states in regions where they are metastable. We show this model to be highly effective when applied to several indirect DEA processes that we studied earlier with brute-force methods. The main advantage of using this model is that one can avoid having to carry out a large number of calculations on metastable anion states; only one or two such calculations are required.

Journal Article↗

PubMed2005

Coulomb-assisted dissociative electron attachment: application to a model peptide.

The fragmentation of positively charged gas-phase samples of peptides is used to infer the primary structure of such molecules. In electron capture dissociation (ECD) experiments, very low-energy electrons attach to the sample and rupture bonds to effect the fragmentation. It turns out that ECD fragmentation tends to produce cleavage of very specific types of bonds. In earlier works by this group, it has been suggested that the presence of positive charges produces stabilizing Coulomb potentials that allow low-energy electrons to exothermically attach to sigma orbitals of certain bonds and thus to cleave those bonds. In the present effort, the stabilizing effects of Coulomb potentials due to proximal positive charges are examined for a small model peptide molecule that contains a wide range of bond types. Direct attachment of an electron to the sigma orbitals of eight different bonds as well as indirect sigma bond cleavage, in which an electron first binds to a carbonyl C=O pi orbital, are examined using ab initio methods. It is found that direct attachment to and subsequent cleavage of any of the eight sigma bonds is not likely except for highly positively charged samples. It is also found that attachment to a C=O pi orbital followed by cleavage of the nitrogen-to-alpha-carbon bond is the most likely outcome. Interestingly, this bond cleavage is the one that is seen most commonly in ECD experiments. So, the results presented here seem to offer good insight into one aspect of the ECD process, and they provide a means by which one can estimate (on the basis of a simple Coulomb energy formula) which bonds may be susceptible to cleavage by low-energy electron attachment.

Alanine↗

PubMed2005

Charge loss in gas-phase multiply negatively charged oligonucleotides.

In an attempt to shed light on the mechanism by which gaseous samples of negatively charged oligonucleotides undergo extremely slow (i.e., over 1-1000 s) charge loss, we have carried out molecular dynamics simulations on an oligonucleotide anion, T(5)(3-), containing five thymine, deoxyribose, and phosphate units in which the first, third, and fifth phosphates are negatively charged. The study is aimed at determining the rate at which an electron is detached from such a trianion by way of an internal Coulomb repulsion induced event. In this process, the intrinsic 5.0-5.1 eV electron binding strength of each phosphate site is reduced by the repulsive Coulomb potentials of the other two negative sites. As geometrical fluctuations cause the distances among the three negative phosphate sites to change, this causes the Coulomb repulsion energies at these sites to fluctuate. Once the Coulomb potential at any phosphate site exceeds ca. 5 eV, the electron on that site is able to undergo autodetachment. Although such an electron must tunnel through a barrier to escape, it is shown that the tunneling rate is not the rate-limiting step in electron loss; instead, it is the rate at which geometrical fluctuations cause the Coulomb potentials to exceed 5 eV that determines the rate of electron loss. Because these rates are extremely slow, special techniques had to be introduced to allow results of dynamics simulations on more flexible models of T(5)(3-) to be extrapolated to predict the behavior of the actual T(5)(3-).

Computer Simulation↗