Current Chemical Biology

Biomarkers and bioprotectors are two of the most innovative techniques to prevent and contrast environmental stress agents. Biomarkers are indicator of normal biological processes or pathogenic processes. Also, they can be indicator or pharmacologic responses to a therapeutic intervention. The World Health Organization (WHO) defined a biomarker as “any substance, structure, or process that can be measured in the body or its products and influence or predict the incidence of outcome or disease” (WHO, International Programme on Chemical Safety. Biomarkers in Risk Assessment: Validity and Validation, 2001). In their report on the validity of biomarkers in environment risk assessment, the WHO has stated that a true definition of biomarkers includes “almost any measurement reflecting an interaction between a biological system and a potential hazard, which may be chemical, physical, or biological. The measured response may be functional and physiological, biochemical at the cellular level, or a molecular interaction.” Bioprotectors against environmental stress agents use a practice of protecting the natural environment and livings, in order to induce a benefit of both the environment and livings. Indeed, environment is being degraded due to humans activity, and the related phisico‐chemical agents can affect humans health. Hence, governments have begun placing restraints on activities that may cause environmental degradation. In particular, scientists are studying protection measures against these environmental stress agents. The aim of this thematic issue is to give a further contribution to describe how harmful action of environmental stress agents on livings, in particular on humans, can be highlighted and contrasted. The results emerging from these contributions should suggest us the direction to plan further research about biomarkers and bioprotectors effectiveness against environmental stress agents.

It is now well known that proteins represent major targets for drug discovery. Drug discovery is based on the concept that drugs bind with the proteins and inhibit their functions, which otherwise become the cause of some diseases. Earlier, it was assumed that proteins had fixed conformation and used to be in a single well-defined state, able to accommodate only one optimal complementary ligand. Such a system corresponded to the “lock-and-key” model of the binding. However, the most important point to consider is that introducing a ligand into the system also changes the environment. It too may affect the most populated state of the protein; such a case would correspond to an “induced-fit” model. It is thought that a single protein structure is only useful to identify ligands for that particular narrow state of the subensemble. However, in order to obtain new leads and properly predict activity of existing inhibitors, multiple structures are the best option. Thus, rather than viewing a protein in a fixed state, it was argued that a protein molecule may exist in a full complement of conformations—most in the native state, some in the induced-fit state, and some in other states. Thus, if the ligand binds preferentially to the induced-fit state with sufficiently favorable free energy, the average structure of the protein will change. Thus, the simplistic “lock and key” model has been superseded by more realistic views of molecular recognition that take into account the intrinsic dynamics of biological macromolecules, which is now called as protein flexibility, and therefore people have started investigating relationship between protein flexibility and binding free energy and presenting some useful hints for understanding when, and to what extent, flexibility should be considered. Protein flexibility is now supposed to be fundamental in the mode of drugreceptor intercations. Various docking methods accounting for protein flexibility have been proposed, tackling problems of ever-increasing dimensionality, as it allows now the increased affinity to be achieved between a drug and its target. Molecular docking is widely used to predict the structure of protein-ligand complexes, and protein flexibility stands out as one of the most important and challenging issues for binding and discovering the potent drugs. However, we are not close to the end of the problem, but just at the beginning. Therefore, this hot topic issue is aimed to present such articles on protein flexibility, invited from potential authors, which may show further directions to researchers to come closer to the problem. As we come closer to problem, we will gain more insight into the drug discovery

No Text Found