Susan K. Gregurick

Terahertz spectra and normal mode analysis of the crystalline VA class dipeptide nanotubes.

Terahertz (THz) vibrational modes are characterized by nonlocal, collective molecular motions which are relevant to conformational changes and molecular functions in biological systems. We have investigated the THz spectra of a set of small bionanotubes which can serve as very simple models of membrane pores, and have examined the character of the THz modes which can impact transport processes. In this work, THz spectra of the crystalline VA class dipeptide nanotubes were calculated at both the harmonic and vibrational self-consistent field (VSCF) level using the CHARMM22 force field with periodic boundary conditions. Comparison of the calculated THz spectra against the experimental spectra revealed that the VSCF corrections generally improved the predictions in the low-frequency region. The improvements were especially manifested in the overall blue-shifts of the VSCF frequencies relative to the harmonic values, and blue shifts were attributed to the overall positive coupling strengths in all systems. Closer examination of the motions in the most significantly coupled normal mode pairs leads us to propose that, when two similar side-chain squeezing modes are coupled, the rapidly increased van der Waals interactions can lead to a stiffening of the effective potential, which in turn leads to the observed blue-shifts. However, we also noted that when the side-chain atoms become unphysically proximate and the van der Waals repulsion becomes too large, the VSCF calculations tend to deviate in the high frequency region and for the system of l-isoleucyl-l-valine. In addition, normal-mode analysis revealed a series of channel-breathing motions in all systems except l-valyl-l-alanine. We show that the inner products of the backbone vibrations between these channel-breathing motions divided the remaining VA class dipeptide systems into two subgroups. It is suggested that these modes may facilitate a pathway for the guest molecule absorption, substitution and removal in the VA class dipeptide nanotubes. Normal mode analysis also demonstrated that the THz motions may contribute to the pore permeability either directly by changing the pore size, or indirectly by affecting the solvent-host effective potentials.

Interaction of GroEL and GroEL/GroES complexes with a nonnative subtilisin variant: a small-angle neutron scattering study

Small-angle neutron scattering and contrast variation were used to study the solution structure of GroEL and GroEL/GroES chaperonins complexed with a nonnative variant of the polypeptide substrate, subtilisin (PJ9). The subtilisin was 86% deuterated (dPJ9) so that it contrasted sufficiently with the chaperonin, allowing the contrast variation technique to be used to separate the scattering from the two components bound in the complex. Both the native double-ring GroEL and a single-ring mutant were used with dPJ9 bound in a 1:1 stoichiometry per GroEL toroid. This allowed both the position and the shape of dPJ9 in the GroEL/dPJ9 complexes to be determined. A single-ring GroEL/GroES variant complexed with one dPJ9 molecule was used to study the structural changes of dPJ9 in GroEL/GroES/dPJ9 complexes formed with ADP and with ATP. It was found that both the shape and the position of the bound dPJ9 in the GroEL/GroES/dPJ9 complex with ADP were the same as those in the GroEL/dPJ9 complex. However, dPJ9 assumed a more symmetric shape when bound in the GroEL/GroES/dPJ9 complex with ATP. This important observation reflects the relative ability of ATP to promote refolding of protein substrates relative to that of ADP.

A dynamics study of the A-chain of ricin by terahertz vibrational calculation and normal modes analysis

We studied the terahertz (THz) spectroscopy and low frequency normal modes of both apo- and holo- (adenosine monophosphate (AMP)-bound) ricin-A-chain (RTA) as a means to understand the dynamical changes that RTA undergoes upon substrate binding. The calculated THz spectra of apo- and holo-RTAs demonstrated a general intensity suppression upon substrate binding, which is attributed to the reduced number of collective motion in THz region. In normal mode analysis of RTA we find a shearing motion that is shared by both the apo- and holo-RTAs, whereas a breathing motion, and an upward hinge rising and an alpha-G bending characteristic motion are dampened significantly upon AMP binding, suggesting these motions are involved in the necessary flexibility of the active site. In contrast, we find a normal mode motion that separates domains I and II of RTA at the interface that is more common in the holo-protein. We hypothesized that the flexibility of the entrance of RTA can facilitate the entry of rRNA and allow the substrate to adjust its conformation and orientation prior to depurination. This process suggests an rRNA binding pathway which is supplemental the current RTA depurination mechanism.

THz Investigations of Condensed Phase Biomolecular Systems

Terahertz (THz) spectroscopic investigations of crystalline dipeptide nanotubes are discussed in the frequency region from 0.6 (2 cm(-1)) to 3 THz (100 cm(-1)). The THz region provides access to collective modes of biomolecular systems and is therefore sensitive to the large scale motions important for understanding the impact of environmental stimuli in biomolecular systems. The focus of this chapter is on THz spectral changes observed in this region when crystals of alanyl isoleucine (AI) and isoleucyl alanine (IA) nanotubes are exposed to water. Of biological significance is the water permeability through hydrophobic pore regions as exemplified in the disparate behavior of these two dipeptide nanotubes. AI is known from X-ray studies and confirmed here to act reversibly to the exchange of water while IA does not accept water into its pore region. Both quantum chemical and classical calculations are performed to better understand the subtle balance that determines guest molecule absorption and conduction through these hydrophobic channels. Examination of the vibrational character of the THz modes with and without water suggests water mode coupling/decoupling with collective modes of the nanotube may play an important role in the permeability dynamics.

A Review of: “Molecular Modelling for Beginners”

This book is Hinchliffe’s most recent contribution to the pedagogical literature of molecular modeling. Hinchliffe states, ‘‘The focus is on Molecular Mechanics, Monte Carlo and Molecular Dynamics.’’ For example, the reader is selectively introduced to MM1 and MM2 (but not MM3 or MM4), and AMBER (but not CHARM). In fact, the book also has a thorough introduction to classical physics and an extensive treatment of molecular quantum mechanics ranging from the semiempirical to the Hartree–Fock (both restricted and unrestricted) level to numerous contemporary post–Hartree–Fock methods such as the G1, G2, and G3 hierarchy. This thoroughness makes this book a powerful addition to the library of any user of molecular modeling methods, because few individuals are knowledgeable of the majority of them. There are few examples given and no problems or exercises accompany the text. The reader of this book (student and professor) must be self-motivated: this is a reasonable although not always fulfilled aspiration for a volume at the level of this book. The reader, however, is given numerous citations to the literature (118 in total), many of which are the pioneering studies themselves but too few are current studies. There are two related features of this book about which the reviewers admit their ambivalence. The first is that although an informal first-person point of view is used for many topics, many methods are described using the original authors’ own words, most often taken from the abstract of ‘‘keynote papers.’’ However, good science and good pedagogy do not always correspond any more than good researchers and good teachers, and beginning students might not be ready to learn from the primary literature whose authorship rarely aims for them. The second is the paucity of chemical examples used to illustrate the more mathematicsand physics-oriented text. This allows the reader to discuss species of direct interest and experience. However, the one molecule that appears with any enthusiasm or frequency, phenylalanine, is consistently misspelled in the text and the index as Mol. Cryst. Liq. Cryst., Vol. 442, pp. 203–205, 2005 Copyright # Taylor & Francis Inc. ISSN: 1542-1406 print=1563-5287 online DOI: 10.1080/154214090964762