Visual pigments are embedded in the disc membranes of the outer segments of vertebrate rods and cones and in the microvilli of invertebrate visual cells. The pigment molecule in both is a most fascinating aggregate of known (the ubiquitous II-cis isomer of vitamin A1 or A2-aldehyde = retinal1 or 2; Hubbard & Wald, 1952) covalently bonded to the unknown (a protein termed opsin) (Anderson, Hoffman & Hall, 1971). This conjugated molecule is called rhodopsin or dehydrorhodopsin (porphryopsin) when the prosthetic portion is retinall or 2 respectively. So sensitive is this sterically hindered, bent and twisted molecule to light that absorption of one photon can initiate its isomerization to the all trans form. This conformational change is but one (but the best known) of the factors leading to receptor membrane changes ushering in the visual impulse.

The cardiac sarcomere is a cellular structure in the heart that enables muscle cells to contract. Dozens of proteins belong to the cardiac sarcomere, which work in tandem to generate force and adapt to demands on cardiac output. Intriguingly, the majority of these proteins have significant intrinsic disorder that contributes to their functions, yet the biophysics of these intrinsically disordered regions (IDRs) have been characterized in limited detail. In this review, we first enumerate these myofilament-associated proteins with intrinsic disorder (MAPIDs) and recent biophysical studies to characterize their IDRs. We secondly summarize the biophysics governing IDR properties and the state-of-the-art in computational tools toward MAPID identification and characterization of their conformation ensembles. We conclude with an overview of future computational approaches toward broadening the understanding of intrinsic disorder in the cardiac sarcomere.

Materials chemistry has been fundamental to the enormous field that encompasses the delivery of molecules both to desired sites and/or at desired rates and durations. The field encompasses the delivery of molecules including fertilizers, pesticides, herbicides, food ingredients, fragrances and biopharmaceuticals. A personal perspective is provided on our early work in this field that has enabled the controlled release of ionic substances and macromolecules. Also discussed are new paradigms in creating biomaterials for human use, the non-invasive delivery of molecules through the skin and lungs, the development of intelligent delivery systems and extensions to nanomedicine. With the advent of potentially newer biopharmaceutics such as siRNA, mRNA and gene editing approaches and their use being limited by delivery, future research in this field may be more critical than ever before.

To talk about enzyme engineering in a context of global problems might seem easy, because the subject is so dynamic and its ramifications so numerous. One might for instance talk about the industrial use of immobilized enzymes to achieve steroid transformations suitable for large-scale production of drugs reducing fertility, or one could describe the application of the same technique for chopping off side-chains of penicillin and other antibiotics as a first step in the production of new semisynthetic drugs, that certainly have a global impact. Or it would be tempting to review the potential of enzyme engineering for synthesizing physiologically active polypeptides that find use in husbandry or medicine.

The origin of pluripotentiality of the immune system in an individual constitutes a major challenge for students of immunology. A vast number of different substances can be shown to be antigenic in an individual, such that their introduction will induce antibody synthesis. These antibodies, mostly detected as serum immunoglobulins, are distinguished by their Capacity for specific combination with the inducer, the antigen. As the specificity of the antibody towards a given antigen can be shown to reside within the amino acid sequence of the molecule by unfolding-refolding experiments (Haber, 1964), it is generally accepted that the antigen-combining capacity of an antibody molecule is under genetic control. So far, studies trying to disclose any unique features of immunoglobulin versus other systems of protein production have failed to do so. No commonly accepted theory yet exists to explain how this multiplicity of immunological potentiality is created at the level of DNA and it is considered beyond the scope of this article to try to cover in detail the various attempts to solve this problem. The reader is referred to a recent review (Lennox & Cohn, 1967) for further details on this subject. It is the intention of the author to describe how pluripotentiality of the immune system operates at the cellular level and to describe and discuss in more detail how regulation of the expression of immunological capacity takes place at the single cell level.

Elastin function is to endow vertebrate tissues with elasticity so that they can adapt to local mechanical constraints. The hydrophobicity and insolubility of the mature elastin polymer have hampered studies of its molecular organisation and structure-elasticity relationships. Nevertheless, a growing number of studies from a broad range of disciplines have provided invaluable insights, and several structural models of elastin have been proposed. However, many questions remain regarding how the primary sequence of elastin (and the soluble precursor tropoelastin) governs the molecular structure, its organisation into a polymeric network, and the mechanical properties of the resulting material. The elasticity of elastin is known to be largely entropic in origin, a property that is understood to arise from both its disordered molecular structure and its hydrophobic character. Despite a high degree of hydrophobicity, elastin does not form compact, water-excluding domains and remains highly disordered. However, elastin contains both stable and labile secondary structure elements. Current models of elastin structure and function are drawn from data collected on tropoelastin and on elastin-like peptides (ELPs) but at the tissue level, elasticity is only achieved after polymerisation of the mature elastin. In tissues, the reticulation of tropoelastin chains in water defines the polymer elastin that bears elasticity. Similarly, ELPs require polymerisation to become elastic. There is considerable interest in elastin especially in the biomaterials and cosmetic fields where ELPs are widely used. This review aims to provide an up-to-date survey of/perspective on current knowledge about the interplay between elastin structure, solvation, and entropic elasticity.

The RNA World hypothesis posits that life emerged from self-replicating RNA molecules. For any single biopolymer to be the basis for life, it must both store information and perform diverse functions. It is well known that RNA can store information. Advances in recent years have revealed that RNA can exhibit remarkable functional versatility as well. In an effort to judge the functional versatility of RNA and thereby the plausibility that RNA was at one point the basis for life, a statistical chemical approach is adopted. Essential biological functions are reduced to simple molecular models in a minimalist, biopolymer-independent fashion. The models dictate requisite states, populations of states, and physical and chemical changes occurring between the states. Next, equations are derived from the models, which lead to complex phenomenological constants such as observed and functional constants that are defined in terms of familiar elementary chemical descriptors: intrinsic rate constants, microscopic ligand equilibrium constants, secondary structure stability, and ligand concentration. Using these equations, simulations of functional behavior are performed. These functional models provide practical frameworks for fitting and organizing real data on functional RNAs such as ribozymes and riboswitches. At the same time, the models allow the suitability of RNA as a basis for life to be judged. We conclude that RNA, while inferior to extant proteins in most, but not all, functional respects, may be more versatile than proteins, performing a wider range of elementary biological functions at a tolerable level. Inspection of the functional models and various RNA structures uncovers several surprising ways in which the nucleobases can conspire to afford chemical catalysis and evolvability. These models support the plausibility that RNA, or a closely related informational biopolymer, could serve as the basis for a fairly simple form of life.

Optogenetics, the use of microbial rhodopsins to make the electrical activity of targeted neurons controllable by light, has swept through neuroscience, enabling thousands of scientists to study how specific neuron types contribute to behaviors and pathologies, and how they might serve as novel therapeutic targets. By activating a set of neurons, one can probe what functions they can initiate or sustain, and by silencing a set of neurons, one can probe the functions they are necessary for. We here review the biophysics of these molecules, asking why they became so useful in neuroscience for the study of brain circuitry. We review the history of the field, including early thinking, early experiments, applications of optogenetics, pre-optogenetics targeted neural control tools, and the history of discovering and characterizing microbial rhodopsins. We then review the biophysical attributes of rhodopsins that make them so useful to neuroscience – their classes and structure, their photocycles, their photocurrent magnitudes and kinetics, their action spectra, and their ion selectivity. Our hope is to convey to the reader how specific biophysical properties of these molecules made them especially useful to neuroscientists for a difficult problem – the control of high-speed electrical activity, with great precision and ease, in the brain.

Since the earliest intelligent history man has tried to understand the origin of life. Some remarkable scientific advances have been made. The concept of natural selection is firmly established as the basis of organic evolution. Advances in the genetic mechanism of inheritance have shed light on the processes and levels at which evolutionary changes occur. Evolution is understood to be a dynamic process, and the organisms present at any given time are those best suited to the environment by virtue of the history of their predecessors. But a deeper question arises: how free is evolution? Are the particular biomolecular structures and processes in existence now in any way uniquely predetermined, or are they the result of a sequence of accidental occurrences?

There is widespread agreement that solar energy is the most promising long-range energy source. However, contemporary technology for bulk energy storage is so primitive that full use of the inevitably erratic solar energy flux is severely limited. Biological systems have perfected methods of storing solar energy for later use in periods of darkness, and it is argued in this symposium presentation that there are many frontiers in biophysics related to the solar energy storage problem. Moreover, the conceivable biological storage systems span a wide range of technology, with appropriate applications in societies of widely varying degrees of industrial development. Use of biological systems to produce hydrogen from solar energy may be among the most versatile of these applications. The entire problem of bioconversion of solar energy presents an excellent example of how the needs for basic scientific understanding and application engineering can be very tightly interwoven.

The following history of the formation of the International Union for Pure and Applied Biophysics (IUPAB) has been assembled from several published accounts in Nature and Science, to which has been added material from the minutes of the meetings of some of the bodies concerned. The introductory paragraphs have been taken from articles by Sutherland (1963) and by Bolt & Sutherland (1960).

Hydrophobic forces are known to have a crucial part not only in the conformation of the three-dimensional structure of proteins, but also in the build-up of DNA–protein complexes. Electric forces also play an important role both in the tertiary as well in the quaternary structure of macromolecular associations. Sometimes both hydrophobic and electric interactions add up their strengths to accomplish these structures but in most cases they act in opposite directions. This fact, together with being overall interactions with different ranges, provides a nuanced equilibrium also modulated by the need to comply with steric hindrances and geometric frustration effects. This review focuses on the utility of using the hydrophobic and electrical dipole moment vectors to describe the interactions that give rise to the structures of biological macromolecules. Although different definitions of both electric dipole and hydrophobic moments have been described in the literature, results obtained in biological assemblies demonstrate the principle of the biological membrane model. According to this model, postulated by our group, biological macromolecules tend to associate by aligning their hydrophobic moments in a similar manner to phospholipids in a membrane. Examples of both closed and open structures are used to assess the predictability of our model. We seek agreement between our results with those described in the current literature. The review ends with possible future projections using this formalism.

The Nobel Workshop ‘Fundamentals of Biomolecular Function: Nucleic Acids, Proteins, and Membranes’, was hosted by the city of Coimbra, Portugal, and the University of Coimbra in May 2005. The workshop focused on three subjects: (i) the functions of biological macromolecules, (ii) the interactions underlying these functions, and (iii) new techniques for studying these interactions. A brief summary of the discussions follows.

RecA family proteins pair two DNAs with the same sequence to promote strand exchange during homologous recombination. To understand how RecA proteins search for and recognize homology, we sought to determine the length of homologous sequence that permits RecA to start its reaction. Specifically, we analyzed the effect of sequence heterogeneity on the association rate of homologous DNA with RecA/single-stranded DNA complex. We assumed that the reaction can start with equal likelihood at any point in the DNA, and that sequence heterogeneity abolishes some possible initiation sites. This analysis revealed that the effective recognition size is five or six nucleotides, larger than the three nucleotides recognized by a RecA monomer. Because the first DNA is elongated 1.5-fold by intercalation of amino acid residues of RecA every three bases, the second bound DNA must be elongated to pair with the first. Because this length is similar to estimates based on the strand-exchange reaction or DNA pair formation, the homology test is likely to occur primarily at the association step. The energetic difference due to the absence of hydrogen bonding is too small to discriminate single-nucleotide heterogeneity over a five- or six-nucleotide sequence. The selection is very likely to be made kinetically, and probably involves some structural factor other than Watson–Crick hydrogen bonding. It would be valuable to determine whether this is also the case for other biological reactions involving DNA base complementarity, such as replication, transcription, and translation.

In this issue, we introduce a new format. To meet reader demand, QRB will augment its long-standing commitment to Reviews with Essays. Essays will be brief, timely commentaries considering one or more of the following: a new idea, a new argument about an old idea, the answer to an outstanding question, a new method, a new interpretation, or a subject otherwise of importance to biophysicists. Whereas Reviews are intellectually rigorous reports that stand as definitive statements on a subject for many years, Essays will seek to apply the same high standard to highlighting a moment in time, to show us where we stand and, so, to infer our trajectory. Essays will appear as deemed appropriate; this inaugural year will be replete with an Essay each quarter. The Board is pleased to announce that our Essayists for 2004 will be Richard Henderson (this issue), Donald Crothers (May), Christopher Miller (August) and Brian Matthews (November).