Role of Trace Nonmetals in Biochemical Systems

2020 ◽  
pp. 231-242
Author(s):  
Pabitra Krishna Bhattacharya ◽  
Prakash B. Samnani
Keyword(s):  
Biochemical Systems

scholarly journals Halogen Bonding: An Underestimated Player in Membrane–drug Interactions

2020 ◽  
Author(s):  
Rafael Nunes ◽  
Diogo Vila Viçosa ◽  
Paulo J. Costa
Keyword(s):  
Drug Discovery ◽  
Chemical Space ◽  
Noncovalent Interactions ◽  
Halogen Bonding ◽  
Lewis Bases ◽  
Protein Ligand Interactions ◽  
Biochemical Systems ◽  
Ligand Interactions ◽  
Dynamics Simulations

<div>Halogen bonds (HaBs) are noncovalent interactions where halogen atoms act as electrophilic species interacting with Lewis bases. These interactions are relevant in biochemical systems being increasingly explored in drug discovery, mainly to modulate protein–ligand interactions. In this work, we report evidence for the existence of HaB-mediated halogen–phospholipid recognition phenomena as our molecular dynamics simulations support the existence of favorable interactions between halobenzene derivatives and both phosphate (PO) or ester (CO) oxygen acceptors from model phospholipid bilayers, thus providing insights into the role of HaBs in driving the permeation of halogenated drug like molecules across biological membranes. This represents a relevant molecular mechanism, previously overlooked, determining the pharmacological activity of halogenated molecules with implications in drug discovery and development, a place where halogenated molecules account for a significant part of the chemical space. Our data also shows that, as the ubiquitous hydrogen bond, HaBs should be accounted for in the development of membrane permeability models.</div>

Epilogue

2021 ◽  
pp. 148-156
Author(s):  
Thomas E. Schindler
Keyword(s):  
Antibiotic Resistance ◽  
Genetic Engineering ◽  
Significant Role ◽  
Living Cells ◽  
Microbial Evolution ◽  
Tree Of Life ◽  
Dna Structures ◽  
Viral Genes ◽  
Biochemical Systems

This chapter reveals the importance of bacterial sex in evolution. After scientists realized that antibiotic resistance and the development of MDR pathogens were caused by bacterial sex, some evolutionary biologists began to wonder about the potential role of HGT in evolution. Scientists speculated that mobile genes might have played a significant role in microbial evolution. James Shapiro has argued genome change in evolution results from a natural genetic engineering process utilizing the biochemical systems for reorganizing DNA structures present in living cells. For billions of years—from the beginning of evolution—bacteria have been transferring genes horizontally, between species and therefore between lineages, interconnecting the branches on the tree of life. The promiscuous process that has scrambled the tree of life is bacterial sex, discovered by Joshua and Esther Lederberg as a laboratory curiosity that helped uncover the molecular secretes of bacterial and viral genes.

The nature of evolution and adaptation: resolving the unity–diversity paradox

1988 ◽  
Vol 66 (5) ◽  
pp. 1146-1152 ◽  
Author(s):  
P. W. Hochachka
Keyword(s):  
Species Diversity ◽  
Current Literature ◽  
Experimental Studies ◽  
Living Systems ◽  
Current Status ◽  
Biochemical Adaptation ◽  
Biochemical Systems ◽  
Regulatory Loci ◽  
Selection For

The concept of the unity of biochemical structures and functions creates the problem for biology of how to account for the pervasive species diversity and obvious adaptedness of living systems. A review of the current literature indicates that four principles, (i) the principle of conservation of critical sequences in both structural and regulatory loci, (ii) the principle of unique assembly of parts via unique (tissue-specific and temporal) activation of regulatory loci, (iii) the principle of genetic innovation via mechanisms internal or external to the genome, and (iv) the principle of biochemical adaptation via selection for favourable alleles of structural and regulatory genes or selection for advantageous genetic innovations, seem capable of resolving the paradox of the unity of biochemical systems despite patently vast species diversity and species adaptation. Evaluation of the current status of each of these principles suggests the especial need for more experimental studies of the role of regulatory loci in species diversification and adaptation.

scholarly journals Evolvability Tradeoffs in Emergent Digital Replicators

2016 ◽  
Vol 22 (4) ◽  
pp. 483-498 ◽  
Author(s):  
Thomas LaBar ◽  
Arend Hintze ◽  
Christoph Adami
Keyword(s):  
Modern Science ◽  
The Other ◽  
Evolution System ◽  
Historical Contingency ◽  
Laboratory Studies ◽  
Digital Evolution ◽  
Replication Machinery ◽  
Biochemical Systems ◽  
The Origin Of Life

The role of historical contingency in the origin of life is one of the great unknowns in modern science. Only one example of life exists—one that proceeded from a single self-replicating organism (or a set of replicating hypercycles) to the vast complexity we see today in Earth's biosphere. We know that emergent life has the potential to evolve great increases in complexity, but it is unknown if evolvability is automatic given any self-replicating organism. At the same time, it is difficult to test such questions in biochemical systems. Laboratory studies with RNA replicators have had some success with exploring the capacities of simple self-replicators, but these experiments are still limited in both capabilities and scope. Here, we use the digital evolution system Avida to explore the interplay between emergent replicators (rare randomly assembled self-replicators) and evolvability. We find that we can classify fixed-length emergent replicators in Avida into two classes based on functional analysis. One class is more evolvable in the sense of optimizing the replicators' replication abilities. However, the other class is more evolvable in the sense of acquiring evolutionary innovations. We tie this tradeoff in evolvability to the structure of the respective classes' replication machinery, and speculate on the relevance of these results to biochemical replicators.

scholarly journals α 2-Adrenoceptors: Challenges and Opportunities—Enlightenment from the Kidney

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
William A. Pettinger ◽  
Edwin K. Jackson
Keyword(s):  
Essential Hypertension ◽  
The Elderly ◽  
Disease States ◽  
Quantitative Monitoring ◽  
Challenges And Opportunities ◽  
Biochemical Systems ◽  
Skin Lightening ◽  
Camp Formation ◽  
Renal Sympathetic

It was indeed a Don Quixote-like pursuit of the mechanism of essential hypertension when we serendipitously discovered α2-adrenoceptors (α2-ARs) in skin-lightening experiments in the frog. Now α2-ARs lurk on the horizon involving hypertension causality, renal denervation for hypertension, injury from falling in the elderly and prazosin’s mechanism of action in anxiety states such as posttraumatic stress disorder (PTSD). Our goal here is to focus on this horizon and bring into clear view the role of α2-AR-mediated mechanisms in these seemingly unrelated conditions. Our narrative begins with an explanation of how experiments in isolated perfused kidneys led to the discovery of a sodium-retaining process, a fundamental mechanism of hypertension, mediated by α2-ARs. In this model system and in the setting of furosemide-induced sodium excretion, α2-AR activation inhibited adenylate cyclase, suppressed cAMP formation, and caused sodium retention. Further investigations led to the realization that renal α2-AR expression in hypertensive animals is elevated, thus supporting a key role for kidney α2-ARs in the pathophysiology of essential hypertension. Subsequent studies clarified the molecular pathways by which α2-ARs activate prohypertensive biochemical systems. While investigating the role of α1-adrenoceptors (α1-ARs) versus α2-ARs in renal sympathetic neurotransmission, we noted an astonishing result: in the kidney α1-ARs suppress the postjunctional expression of α2-ARs. Here, we describe how this finding relates to a broader understanding of the role of α2-ARs in diverse disease states. Because of the capacity for qualitative and quantitative monitoring of α2-AR-induced regulatory mechanisms in the kidney, we looked to the kidney and found enlightenment.

scholarly journals Halogen bonding: an underestimated player in membrane-ligand interactions

2020 ◽  
Author(s):  
Rafael Nunes ◽  
Diogo Vila Viçosa ◽  
Paulo J. Costa
Keyword(s):  
Drug Discovery ◽  
Chemical Space ◽  
Noncovalent Interactions ◽  
Halogen Bonding ◽  
Protein Ligand Interactions ◽  
Biochemical Systems ◽  
Ligand Interactions ◽  
Dynamics Simulations ◽  
Toxicological Activity

<div>Halogen bonds (XBs) are noncovalent interactions where halogen atoms act as electrophilic species interacting with Lewis bases. These interactions are relevant in biochemical systems being increasingly explored in drug discovery, mainly to moduate protein–ligand interactions. In this work, we report evidence for the existence of XB-mediated phospholipid–halogen recognition phenomena as our molecular dynamics simulations support the existence of favorable interactions between halobenzene derivatives and both phosphate or ester oxygen acceptors from model phospholipid bilayers. We also provide insights into the role of XBs in driving the permeation of halogenated small molecules across biological membranes. This represents a relevant molecular mechanism, previously overlooked, eventually determining the pharmacological or toxicological activity of halogenated compounds and hence with implications in drug discovery and development, a place where such species account for a significant part of the chemical space. Our data strongly suggests that, as the ubiquitous hydrogen bond, XBs should be accounted for in the development of membrane permeability models.</div>

scholarly journals Energy-based analysis of biochemical cycles using bond graphs

2014 ◽  
Vol 470 (2171) ◽  
pp. 20140459 ◽  
Author(s):  
Peter J. Gawthrop ◽  
Edmund J. Crampin
Keyword(s):  
Chemical Potential ◽  
Simulation Models ◽  
Bond Graph ◽  
Biochemical Networks ◽  
Engineering Systems ◽  
Bond Graphs ◽  
Secure Foundation ◽  
Biochemical Systems ◽  
Gibb’S Free Energy

Thermodynamic aspects of chemical reactions have a long history in the physical chemistry literature. In particular, biochemical cycles require a source of energy to function. However, although fundamental, the role of chemical potential and Gibb's free energy in the analysis of biochemical systems is often overlooked leading to models which are physically impossible. The bond graph approach was developed for modelling engineering systems, where energy generation, storage and transmission are fundamental. The method focuses on how power flows between components and how energy is stored, transmitted or dissipated within components. Based on the early ideas of network thermodynamics, we have applied this approach to biochemical systems to generate models which automatically obey the laws of thermodynamics. We illustrate the method with examples of biochemical cycles. We have found that thermodynamically compliant models of simple biochemical cycles can easily be developed using this approach. In particular, both stoichiometric information and simulation models can be developed directly from the bond graph. Furthermore, model reduction and approximation while retaining structural and thermodynamic properties is facilitated. Because the bond graph approach is also modular and scaleable, we believe that it provides a secure foundation for building thermodynamically compliant models of large biochemical networks.

Halogen bonding: an underestimated player in membrane-ligand interactions

2020 ◽  
Author(s):  
Rafael Nunes ◽  
Diogo Vila Viçosa ◽  
Paulo J. Costa
Keyword(s):  
Drug Discovery ◽  
Chemical Space ◽  
Noncovalent Interactions ◽  
Halogen Bonding ◽  
Protein Ligand Interactions ◽  
Biochemical Systems ◽  
Ligand Interactions ◽  
Dynamics Simulations ◽  
Toxicological Activity

<div>Halogen bonds (XBs) are noncovalent interactions where halogen atoms act as electrophilic species interacting with Lewis bases. These interactions are relevant in biochemical systems being increasingly explored in drug discovery, mainly to moduate protein–ligand interactions. In this work, we report evidence for the existence of XB-mediated phospholipid–halogen recognition phenomena as our molecular dynamics simulations support the existence of favorable interactions between halobenzene derivatives and both phosphate or ester oxygen acceptors from model phospholipid bilayers. We also provide insights into the role of XBs in driving the permeation of halogenated small molecules across biological membranes. This represents a relevant molecular mechanism, previously overlooked, eventually determining the pharmacological or toxicological activity of halogenated compounds and hence with implications in drug discovery and development, a place where such species account for a significant part of the chemical space. Our data strongly suggests that, as the ubiquitous hydrogen bond, XBs should be accounted for in the development of membrane permeability models.</div>

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