The concept of protein conformational landscape. A) Any protein structure exists in solution as a population of interconverting conformers, shown here as minima on the free energy curve, which represents a one-dimensional cross-section through the high-dimensional energy surface of a protein. In the example given, a population of conformers is composed of three families (A, B, and C). Families are composed of groups of related conformers, while groups, in turn, are composed of yet smaller divisions (not shown). The rates of interconversions are defined by the energy barriers separating alternative conformations. Interconversions on timescales of microseconds and slower usually correspond to large-scale collective (domain) motions within the protein structure, which are relatively rare. Loop motions and side-chain rotations typically occur on timescales of pico- to microseconds, while atom fluctuations occur on timescales of picoseconds and faster. B) Changes in external (environmental) conditions (pH, temperature, pressure, ionic strength, etc.) or in the internal state of the protein (e.g. ligand binding, mutation, posttranslational modification) often lead to redistribution of protein conformers and altered rates of their interconversions, i.e. to a reshaping of protein conformational landscape.

Progress through conflict. Restricted to two-dimensional interpretations by their shared paradigm of reality, round- and square-headed people argue whether an observed aspect of reality is a "circle" or a "square". Although both opposing views are correct, the controversy cannot be resolved without transcending the two-dimensional paradigm and re-conceptualizing reality as being three-dimensional. Because most of the objects in the two-dimensional world of the opponents have square angles, the interpretations of square-headed people are intuitively appealing, seem more believable, and, thus, will be preferred. As a consequence, square-headed people will move up the career ladder and grow in numbers much faster than round-heads. Inevitably, due to the economic principle of least effort, round-heads and their interpretations will be neglected and suppressed, as ignorance and suppression seem to cost less than the efforts of reconciling the seemingly irreconcilable. The ensuing misbalance, manifested as the absence of conflict and widespread complaisance with established order, leads eventually to the belief that reality is what it is known to be by everyone, namely a "square". Books titled "The End of Science" are published and become bestsellers [125]. Such a misbalance blocks the development of collective intelligence, which, by its nature, always proceeds through recurrent conflicts of alternatives/opposites and their constructive resolutions on increasingly higher planes of understanding. No conflict means no resolution. No resolution means no development. No development means stagnation, disease, and degradation. "Not knowing is true knowledge. Presuming to know is a disease. First realize that you are sick; Then you can move towards health." (Lao-Tzu, 600 BC) [126].

Dynamic partitioning of TFIIH in the nucleoplasm. Quantitative visualization and analysis of the fluorescently-tagged transcription factor IIH (TFIIH) molecules in living cells [69] suggest that TFIIH partitions dynamically among at least four distinct molecular pools in the nucleoplasm: a freely diffusing "unemployed" pool, RNA polymerase I and II transcription sites, and DNA repair sites. A) In the absence of DNA damage (UV^-), the average residence times of TFIIH employed in transcription are approximately 25 and 5 seconds for the sites of RNA pol I and II, correspondingly. B) Upon DNA damage (UV⁺), TFIIH reversibly repartitions into DNA repair sites, where its average residence time is significantly longer, 240 seconds, while transcription ceases in the meantime. As the steady-state level of TFIIH in the cell is tightly controlled, the competitive partitioning of TFIIH between different functional pools may potentially couple and coordinate such cellular functions as transcription and DNA repair, both locally and globally. The dynamic partitioning of TFIIH is one of the concrete examples of how the fluxes of moonlighting activities, driven by essentially economic supply-and-demand-type relationships, can lead to a seamless and "design-free" integration of diverse cellular functions into one dynamic and adaptive functional whole that performs and evolves as a self-organizing molecular-scale economy.

The Benard instability. Establishing an increasing vertical temperature gradient (ΔT) across a thin layer of liquid leads to a heat transfer through the layer by conduction (organizational state/form #1). Upon reaching a certain critical value of temperature gradient (ΔT_C), an organizational transition takes place within the liquid layer and conduction is replaced by convection (organizational state/form #2), leading to a stepwise increase in the rate of heat transfer through the layer. The organizational state/form #2 (convection) is a more ordered state (higher negative entropy) than the organizational state/form #1 (conduction). The organizational state/form #2 (convection) will relax into the organizational state/form #1 (conduction) upon decreasing temperature gradient (not shown). As discussed in the text, the Benard instability is an example of a nonequilibrium dynamic system illustrating a number of the universal features shared by all biological (broadly defined) organizations: i) the emergence, maintenance, and development of any biological organization requires a continuous and accelerating flux of energy/matter through biological organization; ii) increasing the rate of energy/matter flux through a biological organization allows for growth in size and/or complexity; iii) any biological organization develops from states of relatively low order (low negative entropy) to states of relatively high order (high negative entropy); iv) increasing the rate of energy/matter flow through a biological organization leads to stepwise organizational state transitions and the emergence of organizational hierarchies and order that cover increasingly larger spatiotemporal scales; v) decreasing the rate of energy/matter flow through a biological organization leads to a stepwise hierarchical relaxation of ordered organization to states of lower negative entropy, and, eventually, to its dissolution and death (see more in the text).

The "trees" and "sponges" theme in biological organization. A) A California oak tree; B, C) Paragorgia corals (coral images courtesy of the National Oceanic and Atmospheric Administration (NOAA) [158]); D) Bronchial tree of the human lung (left half of the cast) and the airways with the pulmonary arteries and veins (right half of the cast) (image courtesy of the author of the cast, Dr. Walter Weber, Institute of Anatomy, University of Bern); E) Arterial system of the human lung (image courtesy of Julius H. Comroe, Jr. [159]); F) White sea sponge (image courtesy of NOAA [160]); G) The freshwater sponge, Spongilla lacustris (image courtesy of Kirt L. Onthank, Washington State University, WA); H) Coral Favites abdita (close up) (kindly provided by Hunterian Museum, ^©Hunterian Museum and Art Gallery, University of Glasgow); I) Scanning electron micrograph of alveolar tissue (image courtesy of Prof. Peter Gehr, Institute of Anatomy, University of Bern); J) Stereo pair of high-voltage electron micrographs showing the structure of the cytomatrix in a cultured NRK cell after rapid freezing (-185°C) and drying from the frozen state (-95°C) (reproduced with permission, ^©Porter, 1984. Originally published in The Journal of Cell Biology. 99: 3s–12s, [130]).