Bioinformatics is an interdisciplinary field of science that develops methods and software tools for understanding biological data, especially when the data sets are large and complex. Bioinformatics uses biology, chemistry, physics, computer science, computer programming, information engineering, mathematics and statistics to analyze and interpret biological data. The subsequent process of analyzing and interpreting data is referred to as computational biology.
Structural biology, as defined by the Journal of Structural Biology, deals with structural analysis of living material at every level of organization. Early structural biologists throughout the 19th and early 20th centuries were primarily only able to study structures to the limit of the naked eye's visual acuity and through magnifying glasses and light microscopes.
In biology and other experimental sciences, an in silico experiment is one performed on a computer or via computer simulation software. The phrase is pseudo-Latin for 'in silicon', referring to silicon in computer chips. It was coined in 1987 as an allusion to the Latin phrases in vivo, in vitro, and in situ, which are commonly used in biology. The latter phrases refer, respectively, to experiments done in living organisms, outside living organisms, and where they are found in nature.
Protein design is the rational design of new protein molecules to design novel activity, behavior, or purpose, and to advance basic understanding of protein function. Proteins can be designed from scratch or by making calculated variants of a known protein structure and its sequence. Rational protein design approaches make protein-sequence predictions that will fold to specific structures. These predicted sequences can then be validated experimentally through methods such as peptide synthesis, site-directed mutagenesis, or artificial gene synthesis.
In the field of molecular modeling, docking is a method which predicts the preferred orientation of one molecule to a second when a ligand and a target are bound to each other to form a stable complex. Knowledge of the preferred orientation in turn may be used to predict the strength of association or binding affinity between two molecules using, for example, scoring functions.
Nuclear magnetic resonance spectroscopy of proteins is a field of structural biology in which NMR spectroscopy is used to obtain information about the structure and dynamics of proteins, and also nucleic acids, and their complexes. The field was pioneered by Richard R. Ernst and Kurt Wüthrich at the ETH, and by Ad Bax, Marius Clore, Angela Gronenborn at the NIH, and Gerhard Wagner at Harvard University, among others. Structure determination by NMR spectroscopy usually consists of several phases, each using a separate set of highly specialized techniques. The sample is prepared, measurements are made, interpretive approaches are applied, and a structure is calculated and validated.
Molecular biophysics is a rapidly evolving interdisciplinary area of research that combines concepts in physics, chemistry, engineering, mathematics and biology. It seeks to understand biomolecular systems and explain biological function in terms of molecular structure, structural organization, and dynamic behaviour at various levels of complexity. This discipline covers topics such as the measurement of molecular forces, molecular associations, allosteric interactions, Brownian motion, and cable theory. Additional areas of study can be found on Outline of Biophysics. The discipline has required development of specialized equipment and procedures capable of imaging and manipulating minute living structures, as well as novel experimental approaches.
Foldit is an online puzzle video game about protein folding. It is part of an experimental research project developed by the University of Washington, Center for Game Science, in collaboration with the UW Department of Biochemistry. The objective of Foldit is to fold the structures of selected proteins as perfectly as possible, using tools provided in the game. The highest scoring solutions are analyzed by researchers, who determine whether or not there is a native structural configuration that can be applied to relevant proteins in the real world. Scientists can then use these solutions to target and eradicate diseases and create biological innovations. A 2010 paper in the science journal Nature credited Foldit's 57,000 players with providing useful results that matched or outperformed algorithmically computed solutions.
Natural computing, also called natural computation, is a terminology introduced to encompass three classes of methods: 1) those that take inspiration from nature for the development of novel problem-solving techniques; 2) those that are based on the use of computers to synthesize natural phenomena; and 3) those that employ natural materials to compute. The main fields of research that compose these three branches are artificial neural networks, evolutionary algorithms, swarm intelligence, artificial immune systems, fractal geometry, artificial life, DNA computing, and quantum computing, among others.
Structure-Based Assignment (SBA) is a technique to accelerate the resonance assignment which is a key bottleneck of NMR structural biology. A homologous (similar) protein is used as a template to the target protein in SBA. This template protein provides prior structural information about the target protein and leads to faster resonance assignment. By analogy, in X-ray Crystallography, the molecular replacement technique allows solution of the crystallographic phase problem when a homologous structural model is known, thereby facilitating rapid structure determination. Some of the SBA algorithms are CAP which is an RNA assignment algorithm which performs an exhaustive search over all permutations, MARS which is a program for robust automatic backbone assignment and Nuclear Vector Replacement (NVR) which is a molecular replacement like approach for SBA of resonances and sparse Nuclear Overhauser Effect (NOE)'s.
Pavel Arkadevich Pevzner is the Ronald R. Taylor Professor of Computer Science and director of the NIH Center for Computational Mass Spectrometry at University of California, San Diego. He serves on the editorial board of PLoS Computational Biology and he is a member of the Genome Institute of Singapore scientific advisory board.
CS-ROSETTA is a framework for structure calculation of biological macromolecules on the basis of conformational information from NMR, which is built on top of the biomolecular modeling and design software called ROSETTA. The name CS-ROSETTA for this branch of ROSETTA stems from its origin in combining NMR chemical shift (CS) data with ROSETTA structure prediction protocols. The software package was later extended to include additional NMR conformational parameters, such as Residual Dipolar Couplings (RDC), NOE distance restraints, pseudocontact chemical shifts (PCS) and restraints derived from homologous proteins. This software can be used together with other molecular modeling protocols, such as docking to model protein oligomers. In addition, CS-ROSETTA can be combined with chemical shift resonance assignment algorithms to create a fully automated NMR structure determination pipeline. The CS-ROSETTA software is freely available for academic use and can be licensed for commercial use. A software manual and tutorials are provided on the supporting website https://csrosetta.chemistry.ucsc.edu/.
Ruth Nussinov is an Israeli-American biologist born in Rehovot who works as a Professor in the Department of Human Genetics, School of Medicine at Tel Aviv University and is the Senior Principal Scientist and Principal Investigator at the National Cancer Institute, National Institutes of Health. Nussinov is also the Editor in Chief of the Current Opinion in Structural Biology and formerly of the journal PLOS Computational Biology.
In computational chemistry, conformational ensembles, also known as structural ensembles, are experimentally constrained computational models describing the structure of intrinsically unstructured proteins. Such proteins are flexible in nature, lacking a stable tertiary structure, and therefore cannot be described with a single structural representation. The techniques of ensemble calculation are relatively new on the field of structural biology, and are still facing certain limitations that need to be addressed before it will become comparable to classical structural description methods such as biological macromolecular crystallography.
Nancy Marie Amato is an American computer scientist noted for her research on the algorithmic foundations of motion planning, computational biology, computational geometry and parallel computing. Amato is the Abel Bliss Professor of Engineering and Head of the Department of Computer Science at the University of Illinois at Urbana-Champaign. Amato is noted for her leadership in broadening participation in computing, and is currently a member of the steering committee of CRA-WP, of which she has been a member of the board since 2000.
Bonnie Anne Berger is an American mathematician and computer scientist, who works as the Simons professor of mathematics and professor of electrical engineering and computer science at the Massachusetts Institute of Technology. She is the head of the Computation and Biology group at MIT's Computer Science and Artificial Intelligence Laboratory. Her research interests are in algorithms, bioinformatics and computational molecular biology.
G. Marius Clore MAE, FRSC, FRS is a British-born, American molecular biophysicist and structural biologist. He was born in London, U.K. and is a dual U.S./U.K. Citizen. He is a Member of the National Academy of Sciences, a Fellow of the Royal Society, a NIH Distinguished Investigator, and the Chief of the Molecular and Structural Biophysics Section in the Laboratory of Chemical Physics of the National Institute of Diabetes and Digestive and Kidney Diseases at the U.S. National Institutes of Health. He is known for his foundational work in three-dimensional protein and nucleic acid structure determination by biomolecular NMR spectroscopy, for advancing experimental approaches to the study of large macromolecules and their complexes by NMR, and for developing NMR-based methods to study rare conformational states in protein-nucleic acid and protein-protein recognition. Clore's discovery of previously undetectable, functionally significant, rare transient states of macromolecules has yielded fundamental new insights into the mechanisms of important biological processes, and in particular the significance of weak interactions and the mechanisms whereby the opposing constraints of speed and specificity are optimized. Further, Clore's work opens up a new era of pharmacology and drug design as it is now possible to target structures and conformations that have been heretofore unseen.
Structural chemistry is a part of chemistry and deals with spatial structures of molecules and solids. For structure elucidation a range of different methods is used. One has to distinguish between methods that elucidate solely the connectivity between atoms (constitution) and such that provide precise three dimensional information such as atom coordinates, bond lengths and angles and torsional angles.
Daniel Mier Gusfield is an American computer scientist, Distinguished Professor of Computer Science at the University of California, Davis. Gusfield is known for his research in combinatorial optimization and computational biology.
Mona Singh is the Wang Family Professor in Computer Science in the Lewis-Sigler Institute for Integrative Genomics and the Department of Computer Science at Princeton University. She is Editor-in-Chief of the Journal of Computational Biology.
