Recent developments in methodologies for calculating the entropy and free energy of biological systems by computer simulation

The Helmholtz free energy, F, plays an important role in proteins because of their rugged potential energy surface, which is 'decorated' with a tremendous number of local wells (denoted microstates, m). F governs protein folding, whereas differences DeltaF(mn) determine the relative populations of microstates that are visited by a flexible cyclic peptide or a flexible protein segment (e.g. a surface loop). Recently developed methodologies for calculating DeltaF(mn) (and entropy differences, DeltaS(mn)) mainly use thermodynamic integration and calculation of the absolute F; interesting new approaches in these categories are the adaptive integration method and the hypothetical scanning molecular dynamics method, respectively.     

Concept of energy in biological systems

Beside the concept of material inputs and outputs of components of the representation of biological systems given to us by Rosen, the concept of energy is incorporated. The interaction of material and energy is represented by a cartesian product; and separate material and energetical mappings are considered as the new representation of components. These developments generate aMα category, and it is shown thatMα is isomorphic to theM category of previous developments.     

Free energy of biological systems

The generalization of the Gibbs potential to open spatially inhomogeneous systems is given. This generalization is based on the abandonment of the local equilibrium hypothesis and the introduction of the specific parameters of spatial inhomogeneity: thermodynamical forces and the coordinates of useful works. The existence of the potential state function whose decrease determines the algebraic sum of useful (external) and dissipative (internal) works executed by the system was justified. This function presents the difference between the internal energy of the spatial inhomogeneous system and its homogeneous parts and was named (owing to its independence from the pathways of processes in the space of thermostatic variables) the general thermodynamic potential. It was demonstrated that the application of this potential to biological systems permits one to trace their development for each of their intrinsic degrees of freedom, to combine the thermodynamic and kinetic approaches to the problems of their evolution, to find a criterion of maturity of a biological organism and a general measure of the orderliness of the biosystem, to find the driving forces of biological processes, and confirm the possibility of development of biosystems without the equilibrium state.     

Recent developments in the monitoring,modeling and control of biological production systems

Current trends in the development of methods for monitoring, modeling and controlling biological production systems are reviewed from a bioengineering perspective. The ability to measure intracellular conditions in bioprocesses using genomics and other bioinformatics tools is addressed. Devices provided via micromachining techniques and new real-time optical technology are other novel methods that may facilitate biosystem engineering. Mathematical modeling of data obtained from bioinformatics or real-time monitoring methods are necessary in order to handle the dense flows of data that are generated. Furthermore, control methods must be able to cope with these data flows in efficient ways that can be implemented in plant-wide computer communication systems.Mini-review for the proceedings of the M3C conference     

The surface energy of water: the largest but forgotten source of energy in biological systems

Many functional proteins perform mechanical, structural or chemical work. Such proteins often use the energy from the hydrolysis of adenosine triphosphate (ATP). The role of ATP as an energy source and its production by metabolism was established in the middle of the twentieth century and replaced glycolysis as the focus of study. Before this time the surface energy of water, quantified in the middle of the nineteenth century, had been visualized as an important source of biological energy. Experimental and theoretical work has shown that the internal work done by this energy source may greatly exceed the energy derived from metabolism. Although the energy from ATP usually does the work external to the body, even this may be supplemented by the surface energy of water to give greater efficiency. The consideration of the principles by which proteins might employ this larger source of energy to do work is germane at this time.     

Concept of energy in biological systems and the effects of irradiations of low energies on enzyme-substrate systems

The recent mathematical formalization of the concepts of matter and extrinsical energy, which are used for the relational representation of biological systems, is employed in the analysis of the important experimental discoveries of Comorosanet al. related to low energy electromagnetic irradiations on enzyme substrates. By means of the present analysis one of the properties inherent to the experimental phenomena is more precisely exposed, and theoretical developments corresponding to “energetical evolutions” in a biological system (Leguizamón, 1976) may now have an experimental basis. Important limitations are introduced for the validity of the commutativity and associativity of cartesian product of sets, when they represent matter and its linked extrinsical energy. In connection with this last aspect, new important knowledge is obtained for the relational mathematical representation of biological systems.     

Pro-oxidative effect of peroxynitrite regarding biological systems: a special focus on high-molar-mass hyaluronan degradation

Current understanding on the role of peroxynitrite in etiology and pathogenesis of some human diseases, such as cardio-vascular diseases, stroke, cancer, inflammation, neurodegenerative disorders, diabetes mellitus and diabetic complications has recently led to intensive investigation of peroxynitrite involvement in physiology and pathophysiology. Mechanism of cytotoxic effects of peroxynitrite involve its reactions with lipids, DNA/RNA, proteins, and polysaccharides, thus triggering cellular responses ranging from subtle changes of cell functioning to severe oxidative damage of the affected macromolecules leading to necrosis or apoptosis. The present work is aimed at providing a brief overview of i) peroxynitrite biosynthesis and reaction pathways in vivo, ii) its synthetic preparation in vitro, and iii) to reveal its potential damaging role in vivo, on actions studied via monitoring in vitro hyaluronan degradation. The complex biochemical behavior of peroxynitrite is determined by a number of variables, such as chemistry of the reaction itself, depending mostly on the involvement of conformational structures of different energy states, concentration of the species involved, content of reactive intermediates and trace transition metal ions, contribution of carbon dioxide, presence of trace organics, and by the reaction kinetics. Recently, in vitro studies of oxidative cleavage of hyaluronan have, in fact, been the subject of growing interest. Here we also describe our experimental set-up for studying peroxynitrite-mediated degradation of hyaluronan, a system, which may be suitable for testing prospective pharmacological substances.     

Recent developments in multiscale free energy simulations

Physics-based free energy simulations enable the rigorous calculation of properties, such as conformational equilibria, solvation or binding free energies. While historically most applications have occurred at the atomistic level of resolution, a range of advances in the past years make it possible now to reliably cross the temporal, spatial and theory scales for the modeling of complex systems or the efficient prediction of results at the accuracy level of expensive quantum-mechanical calculations. In this mini-review, we discuss recent methodological advances as well as opportunities opened up by the introduction of machine learning approaches, which tackle the diverse challenges across the different scales, improve the accuracy and feasibility, and push the boundaries of multiscale free energy simulations.     

Removing ambiguity from the biological species concept

The biological species concept (BSC) is a common way to define species although it is ambiguous even when strictly applied. I interpret it here syntactically in four different ways and show that one of them is more suitable than previously thought. The first interpretation (fully restricted) produces discrete, non-overlapping biological species with the inconvenience of being inapplicable when there is gradual evolution of reproductive isolation. The second (cohesion relaxed) and fourth (fully relaxed) interpretation are overly unrestricted to be useful. The third interpretation (isolation relaxed) overcomes the problem of gradual evolution of reproductive isolation at the cost of recognizing non-discrete, overlapping biological species. That is, some populations are members of more than one species. Non-discreteness, however, removes hand-waving in infamous difficulties of the BSC such as those with ring species, phyletic species, and syngameons. Moreover, it lets the BSC deal with introgression with no appeal to subjectivity. Therefore, precision in terms underlying the BSC provides an objective and still natural alternative to deal with gradual evolution of reproductive isolation.     

A new proposal regarding the transport mechanism of mercury in biological membranes

The interactions of mercury (Hg²⁺) with biological membranes have been investigated. The experimental results indicate that Hg²⁺ induces a rapid alkalinization in energized Lysosomes from rat liver. The interpretation of the process is that the mercury enters the Lysosomes as a Hg(OH)₂ electroneutral compound, thus inducing alkalinization in the matrix.     

The concept of biological control methods in aquaculture

Microbial techniques of biocontrol using the interaction ofmicroorganisms to repress the growth of deleterious bacteria andviruses were developed. The bacterial strain used in this work alsoimproved the growth of fishes and crustaceans. Using the conceptandprocedures of the biocontrol method described here, the aquacultureproduction became stable and evenincreased.     

Expression systems and developments in plant-made vaccines

Delivery of vaccines to mucosal surfaces can elicit humoral and cell-mediated responses of the mucosal and systemic immune systems, evoke less pain and discomfort than parenteral delivery, and eliminate needle-associated risks. Transgenic plants are an ideal means by which to produce oral vaccines, as the rigid walls of the plant cell protect antigenic proteins from the acidic environment of the stomach, enabling intact antigen to reach the gut associated lymphoid tissue. In the past few years, new techniques (such as chloroplast transformation and food processing) have improved antigen concentration in transgenic plants. In addition, adjuvants and targeting proteins have increased the immunogenicity of mucosally administered plant-made vaccines. These studies have moved plant-made vaccines closer to the development phase.