> # 🐜 > ### One of the most fascinating topics in life sciences lies in the understanding of the processes of ==self-assembly of supramolecular architectures.== > 🇮🇹 **Maurizio Brunori & Stefano Gianni**^[Brunori M, Gianni S. An Outlook on the Complexity of Protein Morphogenesis in Health and Disease. Frontiers in Molecular Biosciences. 2022 Jun 13;9:909567.] <br> Most people stop at the realm of "small molecules," Proteins dedicate and create almost every cellular process imaginable. The field of protein science remains extensively studied to date and continues to offers truly novel ways into the management of disease for just about every ontology known.^[Kumar V, Barwal A, Sharma N, Mir DS, Kumar P, Kumar V. Therapeutic proteins: developments, progress, challenges, and future perspectives. 3 Biotech. 2024 Apr;14(4):112. [DOI Kumar 2024](https://doi.org/10.1007/s13205-024-03958-z)] However, these submicroscopic, meaning normal microscopes using light can't resolve them in resolution, multi-linked amino acid manifestations are hardly known as part of pop culture. In that right, this manuscript dedicates itself to addressing the atoms which form the basis of amino acids, to amino acids and their specific combination, or ==permutative== to describe it, properties to permit ==protozoan==, that being single-cell, and ==metazoan==, or multicellular organisms, to proliferate and flourish. > #### By examining the cell and its structure visually, it's found time and time again that the living things we can't see deploy the same molecular tricks as us. And while this is a humbling fact, we need to appreciate that the entire human population, between person to person, is matched in an unimaginably exact developmental pathway, too. Proteins are life-sustaining as most of the relevant genetic parts of DNA harbors genes, which complete the necessary steps to create polypeptide tools for the common cell to defy irreversible fates like cell death, uncontrolled growth, and the human health nexus at large.^[Feuermann M, Mi H, Gaudet P, Muruganujan A, Lewis SE, Ebert D, Mushayahama T, dictyBase, Chisholm Rex L. Fey Petra, Giglio Michelle, Nadendla Suvarna. A compendium of human gene functions derived from evolutionary modelling. Nature. 2025 Feb 26:1-9.] It can be said that proteins are intimately a part of the ==autopoietic== character of cells, meaning a cell's traits like self-creating, -maintaining, and -containing,^[Villalobos M. Living beings as autopoietic bodies. Adaptive Behavior. 2020 Feb;28(1):51-8.] as they function as molecular mediators between everything. If DNA is the "blueprint" of life, then proteins are function derived from which the blueprint calls for: the tools, parts, structure, what have you, to get the job done. When we see ourselves and others in something like a photo, we should be really attributing the complete catalysis produced by these biopolymers in every day life. And while this 'mechanistic' analogy is easy to understand and explain for the sake of proteins, they should not be confused as "machine-like" cell assemblies as it paints their place in the life and tie to a meaningful existence unfaithfully. Proteins are a globally observed phenomenon. These substances are found behaving like liquid anti-freeze by stopping the formation of ice to withstanding the fierce heat up to 250-degrees Farenheit. >  > **De novo, or created from scratch proteins. Most "de novo" proteins are created in specialized software by computers. From nanocages, to letters and numbers.**^[Ingraham JB, Baranov M, Costello Z, Barber KW, Wang W, Ismail A, Frappier V, Lord DM, Ng-Thow-Hing C, Van Vlack ER, Tie S. Illuminating protein space with a programmable generative model. Nature. 2023 Nov 30;623(7989):1070-8.] --- ##### Keywords _Amino Acid, Sequence, Secondary Structure, Protein Dynamics, Kinetic Landscape_ --- <br> # Amino Acids in 0-D Zero dimensions, abbreviated 0-D, are necessary to understand one thing at a time by not relating anything other but the essence of the thing at hand. This is also meant literally, by not including the use of three-dimensional measures like length, width, and height. Approaching the wild true-to-reality behavior of proteins in 0-D when breaking down the opportunity to understand their nature should only be by according to their name, abbreviation, or symbol. This firsthand representation by introducing the vital pieces that belong to protein by name avoids an overloading explaination for those not already familiar with the topic. ## They're Building Blocks Amino acids are the individual building blocks of proteins. They cannot be broken down any further without losing their characteristic properties that pertain to polypeptides. If broken down further, these amino acids would no longer behave as they would in real-life biology, and without select atoms, the properties of these small molecules would change due to a change in their chemical identity. > > **All 20 amino acids in 3D, represented by the ball-and-stick model with their three-letter abbreviation.**^[Nadzirin N, Willett P, Artymiuk PJ, Firdaus-Raih M. IMAAAGINE: a webserver for searching hypothetical 3D amino acid side chain arrangements in the Protein Data Bank. Nucleic acids research. 2013 Jul 1;41(W1):W432-40.] These essential building blocks are not only found in every single lifeform imaginable but are also part of non-living microbes like viruses.^[Koonin EV. On the origin of cells and viruses: primordial virus world scenario. Annals of the New York Academy of Sciences. 2009 Oct;1178(1):47-64.] It can be said, for our example of viruses, that they're only around due to hijacking what proteins are made by the cell when infected. So not only are proteins not alive, but they permit non-living systems to exist, and when large enough in size, allow living systems to exist, too. In that way, proteins share a core part of developmental philosophy, how things grow as unimaginably well-controlled concerts with discrete and countless trajectories; proteins share a unique journey between it all. ## Twenty Amino Acids For everything alive, to have been alive, extinct, or even later to live as part of the same or newly developing species only requires 20 amino acids. It is likely true that earlier forms of life may have experienced problem solving on the molecular level with less amino acids, however, today, every organism known can be analyzed to find that they contain just 20.  The power is a unique ability for each amino acid to participate in the final three-dimensional structure of a protein, and not only this, but their ability to form in space via astrobiology continues to be investigated. Almost every amino acid, at 14, have been found, not in one space rock, but from the analysis of several to determine they do in fact form in space.^[Wang,Y. (2025). Evidence of the Existence of Proteinogenic Amino Acids in Space. Applied and Computational Engineering,143,42-46.] However, their capacity to covalently bond with each other, granting countless properties for cells and living systems to benefit, do not form in asteroids and neither meteorites. This makes proteins exceptionally rare and just about statistically impossible to spontaneously form elsewhere. Because there are 20 standard, canonical, or otherwise commonly found amino acids here on Earth, researchers in the field of protein science have assigned symbols, or letter codes like an alphabet, to each amino acid to keep things short. We'll get into the details of why an abbreviation or symbol does a better job for select representations over spelling out the amino acid in full. ## Required Assembly Amino acids on their own are commonly floating around in the cell with most actively binding and captured to be held-in-place like a glove by another another molecule called mRNA. The lowercase M (m-) is an initialism for "messenger" as a function of the RNA molecule. It operates as a cartridge to hold a single amino acid to be prepared like a cassette, offloaded onto a significantly more large, multi-biomolecular complex called a ribosome. # Primary Sequence in 1-D Single amino acids on their own don't exhibit the beautifully intericate behaviors of their polymer counterparts. By covalently stitching single amino acids together in a chain, an amino acid sequence is formed, which is the 1-D representation of proteins in a line or sequence. Sequences are read from left-to-right according to their terminals, or where the protein sequence starts and ends. >  > **Comparing the sequences in which amino acids are chained together across species. Here, the amino acid sequence is read from left-to-right.** # Skeletal Structure in 2-D Skeletal formulas are essential to understanding how molecules are covalently bonded. In order to appreciate the long amino acid sequences in nature, skeletal structures are vital to understand their steric geometries which in turn translate into function. Amino acid geometry and their bonding arrangements determine how protein domains work which fuel life.   >  > **Skeletal formula for a short protein found in horse muscle called apomyoglobin placed planar, or flat for the viewer, without folding. Its sequence, reading it visually from left to right, is Gly-Leu-Ser-Asp-Gly-Trp-Gln-Gln-Val, or sequence GLSDGWQQV.** # Secondary Folding in 3-D Finalized folding usually entails the formation of secondary structures. This is where an amino acid sequence that's flat and 2-D becomes 3-D by folding on itself to form shapes. >  > **Two common secondary structural patterns found in protein: an alpha-helix and beta-sheet.** ## Special Spots: Domains Domains are the areas, whether on the surface or inside of a protein that are characterized to have a role or function. When a protein is studied, special attention is focused on the specific amino acids in a protein's sequence which correlate to a corresponding function. Not all amino acids of a protein are found to participate in its unique function, so in that way, the term domain is specific to what part or parts of a protein exhibits a special trait unique to their sequence. If a protein is found to create the oxygen we breathe, then it can be considered an 'oxygen creating' domain. If there's a protein that experimentally reduces the number of bacterial pathogens on a surface, say in a hospital or clinical setting, then the protein and its domain which grants this ability is studied and could be referred to as a 'pathogen killing' domain. # Tertiary Landscape in 4-D The forth dimension (4-D) includes time, which also encompasses one of the problems with proteins: they move and aren't static. Capturing this movement, say by video, is still an area of study. Otherwise, almost all pictures of protein to date are just one single frame of a protein's incredibly active life on this scale. Pictures of protein in any fashion can be thought of as a portrait of someone: they represent the look of the person at the time, but this person has an entire life beyond the picture itself. Proteins are still only best illustrated by single snapshots, which only gives a snippet of their dynamics. This is why microscopy techniques of the 21st century aim to include the 4th-dimension: time, to better understand how proteins move and shape-shift so readily to obtain their function in cells. >  > **There are desirable and more desirable configurations for a protein. It is a necessary part of a protein's journey to transverse this folding landscape, to not only the second-best folding, but to find the best folding possible for healthy function.** ## Nuclear Magnetic Resonance Usually just called NMR, is one of the best ways to study the fast paced dynamics of a protein on this scale. It instead images multiple shots of a protein in order to capture a playthrough of its movement. # Quaternary Recruitment Once the tertiary structure of a protein is stabilized, it can form contacts with other neighboring proteins to form complexes. A protein complex is said to be the quaternary-level structure in the protein structure heirarchy, where some proteins may only be capable of just folding on itself without binding to other proteins, thereby remaining in the tertiary-level form. >  > **Proinsulin; human insulin monomer, dimer, and full multimer.**^[Hilgenfeld R, Seipke G, Berchtold H, Owens DR. The evolution of insulin glargine and its continuing contribution to diabetes care. Drugs. 2014 Jun;74(8):911-27.] ## Protein-Protein ## Nucleic Acid-Protein Forms *Tobacco Mosaic Virus* ## Lipid-Protein *BAR Domain Proteins*