Current Physical Chemistry - Volume 3, Issue 1, 2013

This short review is formed on the basis of the great contributions for the section: Quantum Nanobiology and Biophysical Chemistry to appear in Current Physical Chemistry. The review is concerned with problems and perspectives of Molecular Biophysics of today and especially with respect to quantum aspects.

Biological macromolecules evolved over billions of years to achieve dynamic structures adapted to their function. Appropriate structure and appropriate dynamics are necessary for biological activity. Intra and inter protein interactions are modulated by weak forces, which depend sensitively on the environment. These forces define the active fold of the macromolecule and also its dynamics about the time-average structure. Dynamics, however, is more sensitive than structure to environmental factors such as solvent, temperature or pressure. Because of inappropriate dynamics, a macromolecule can be inactive in conditions in which its correct structure is maintained and stable. It is essential, therefore, to take into account the environmental context in experimental or simulation studies of protein dynamics. Neutron scattering can provide unique experimental data to underpin molecular dynamics calculations in this context.

The lamellar lipid-bilayer component of cell membranes is a complex self-assembled macromolecular aggregate that hosts a large part of the cell's biological activity such as signal transduction, energy- and materials transport, as well as communication with the environment. The structure, dynamics, and stability of the lipid bilayer are controlled by thermodynamic forces leading to overall tensionless bilayers with a conspicuous lateral pressure profile and build-in curvature-stress instabilities that may be released locally or globally in terms of morphological changes leading to the formation of non-lamellar and curved structures. A key controller of the bilayer's propensity for forming curved structures is the average molecular shape of the different lipid molecules. The molecular shape mediates, via the curvature stress, a coupling to membrane-protein function. The present mini-review provides a status of the field with a focus on how curvature and curvature stress as an emergent property of a macromolecular assembly may furnish an understanding of biological activity at membranes. An example is given of how this insight can be transferred into technology.

Modelling how proteins bind to one another is a challenging task, in part due to the conformational changes that can occur upon complex formation. We here describe the various types of motion that occur upon protein binding and discuss their treatment in computational protein-protein docking methods to predict the structure of the bound complex. Considered are five different categories of structural change, that cover timescales from picoseconds to milliseconds and amplitudes extending to tens of angstroms. First small-scale motion, which includes bond stretching, bond angle bending and dihedral rotation is addressed. This is followed by larger motions of the protein main-chain, the loops and entire protein domains. Finally, we consider the class of intrinsically disordered proteins including protein segments that refold upon binding. For each category, the capabilities and limitations of current docking procedures are discussed by means of an illustrative example.

In this work we have used Fourier transform infrared (FTIR) / vibrational absorption (VA) spectroscopy to study two cancer cell lines: the Henrietta Lacks (HeLa) human cervix carcinoma and 5637 human bladder carcinoma cell lines. Our goal is to experimentally investigate biochemical changes and differences in these cells lines utilizing FTIR spectroscopy. We have used the chemometrical and statistical method principal component analysis (PCA) to investigate the spectral differences. We have been able to identify certain bands in the spectra which are so-called biomarkers for two types of cell lines, three groups for the 5637 human bladder carcinoma cell line (5637A, 5637B and 5637C), and another one for the HeLa human cervix carcinoma cell line. The vibrational modes can be assigned to specific bands involving characteristic motions of the protein backbone. This work shows that infrared vibrational absorption (VA) spectroscopy can be used as a useful tool in medical diagnostics that provides in principle additional information and detail to that which can be obtained/provided from conventional histological studies, and more conventional mass spectroscopic and NMR techniques. The use of high level vibrational spectroscopic simulation, in addition to the chemometric and statistical tools of PCA, linear and quadratic discriminant analysis, and artificial networks methods that are good at finding correlations, but provide little if any physical, chemical and biochemical insight into the nature of the changes at a molecular level, is also strongly advocated and helpful to gain more physical, chemical and biological insight. Hence the combination of vibrational spectroscopic simulations and experimental vibrational absorption spectroscopy and imaging are advocated for future developments in this field.

Redox proteins and enzymes containing iron-sulfur clusters continue to emerge as key elements of cellular metabolism. Proteins and clusters of enormous complexity continue to succumb to experimental definition, such as nitrogenase and hydrogenase enzymes. Simpler systems, including iron-sulfur clusters of the general formula FexSy(SCys) z, have long been subject to fundamental research, including the theoretical modeling of cluster redox potential in variable protein environments. In this review, we explore results obtained on these systems, which are only relatively simple. If the efforts reviewed continue to flourish, they can form the foundation for methods and basic physical principles relevant to the most complex systems.

Over the past 10-15 years LNA (Locked Nucleic Acid) has taken a central position in nucleic acid chemistry and biology. The enhanced hybridization properties against both DNA and RNA have become a new reference in the field and proven to be enabling for many application in life sciences. For therapeutic use as RNA targeting drugs LNA enable the design of potent antisense oligonucleotides. Much effort has been dedicated to get efficient delivery of RNA targeting drugs, but in contrast to e.g. siRNA duplexes it has been demonstrated that LNA oligonucleotides are taken up by cells without added deliver vehicles in an active state (gymnotic delivery). Here, the fundamental properties of LNA are reviewed together with the recent and most advanced pre-clinical/clinical LNA data.

One remarkable aspect of small globular proteins folding process is the fastness. However, different proteins of similar sizes may paradoxically present folding rates that differ by several orders of magnitude. In the present work we show how reliably a specific minimalist lattice model can reproduce such large range of folding characteristic times during the search stage of the protein folding process. We select nine representative protein-like (compact) structures, which illustrate distinct combinations of cooperative and non-cooperative structural patterns. The respective sequences of residues are designed by a general rule, and then submitted to extensive Monte Carlo simulations to determine the characteristic folding time of each target structure. Our results reproduce the experimentally observed exponential-like folding kinetics --of small, two-state globular proteins, and strongly support the idea that the search mechanism for the native structure is fully governed by the hydrophobic effect and steric constraints. The present results are achieved through the application of nonextensive statistical mechanics.

Superconductivity is described by the well-known Bardeen-Cooper-Schrieffer (BCS) theory, which is a symmetry breaking approximation. Color superconductivity shows up in extremely high density matter and temperature, which is here investigated and compared to the other end of the scale of low energy/temperature of organic superconductors. An approach to color superconductivity conciliating the BCS theory with the color SU(3) symmetry, the cornerstone of the rigorous theory of the strong interaction, Quantum Chromo-Dynamics (QCD), is used to describe the superconducting phase. The magnetization of a high density relativistic fluid of elementary particles is studied. We find that the magnetic field of spin polarized matter with densities of 2 to 3 ρ0 , where ρ0 is the equilibrium density of nuclear matter, is rather huge, of the order of 1017 Gauss. Finally we look at the chiral nature of nuclear forces and interactions as they possibly relate to chirality of nuclei (atoms) in molecules as a source of chirality in amino acids and hence in life. Previous works have not investigated the nuclear forces as a possible bias which initiated the bias towards L-amino acids as the building blocks on proteins, and later life.

An extensive conformational analysis of 2´,3´-didehydro-2´,3´-dideoxythymidine (stavudine, d4T), a nucleoside reverse transcriptase inhibitor widely used in anti-retroviral therapy, is presented. At 298.15 K all 19 allowed d4T conformers are within the 5.51 kcal/mol Gibbs free energy range. Eight types of specific intramolecular interactions, which govern the conformational properties of d4T, were identified, namely: O5´H···O2, C1´H···O2, C6H···O5´, C6H···O4´, C5´H1···O2, C5´H2···O2, C6H···H1C5´ and C2´···O2. The results confirm the current point of view that the biological activity of d4T is, most likely, connected with termination of the DNA chain synthesis in the 5´-3´ direction. Thus, d4T competes with canonical thymidine for binding to the HIV-1 reverse transcriptase active site.

We consider here the electronic deactivation pathway/process of the carotenoid-chlorophyll complex following photoabsorption/activation. We point out the reasoning why the conventional Foster-Dexter (FD) approach, or deexcitation via tunneling, or paths through conical intersections are not compatible with all experimental data for this system. The proposed Bio-Auger (B-A) process discussed in connection with deactivation of the electronically excited thymine dimer when bound to the photolyse protein (photoactivated photolyase-protein complex) provides a suitable understanding of all observed experimental facts/data, that is, of all charge and energy transfers, radiationless transitions, and the overall de-excitation process. In addition, it leads to a current loop in the two light harvesting complexes: LHI and LHII. The current loop in LHII generates a magnetic field in the reaction center (RC) located inside that loop. Thus, electrons and other charged particles in the RC will move in one particular direction, as experimentally observed.

A method of analytical prediction (AP) and the corresponding index LAP used for predicting high-spin stability of alternant conjugated hydrocarbon radical polymers were generalized for both non-disjoint closed-type and open-type systems. The general formulas of LAP were derived analytically as the function of the number of unpaired electrons, denoted as N, without performing any localization procedure to attain the minimum mixing between nonbonding molecular orbitals (NBMOs). To examine the reliability of this analytical treatment, the relationship between the LAP and the energy stability in high-spin state was investigated by ab initio method for open-shell systems. It was shown that this approach can be a useful tool for qualitative prediction of ferromagnetism in alternant conjugated hydrocarbon radical polymers.

The bio-protective properties of monosaccharaides, namely mannose, fructose and fucose, on the stability and dynamical properties of the NMR determined hen egg-white lysozyme structure have been investigated by means of molecular dynamics simulations at room temperature in aqueous solution and in 7 and 13 wt % concentrations of the three sugars. Results are discussed in the framework of the bio-protective phenomena. The three sugars show similar bioprotective behaviours at room temperature (300 K) in the concentration range studied as shown by the small RMSDs of the resulting MD structures from that of starting NMR structure. The effects of sugars on protein conformation are found to be relatively strong in that the conformation of lysozyme is stable after an initial 9 ns equilibration for fucose and mannose and 12 ns equilibration for fructose, respectively, at high concentrations. For mannose the final RMSD is significantly smaller than that of fucose and fructose at the higher concentration, while at the lower concentration the RMSD are essentially the same. The radial distribution function of the water and sugars around lysozyme was used to monitor the preferential hydration. Analysis of the solvent and sugar distributions around lysozyme was used to investigate the interfacial solvent and sugar structure near the protein surface.