In silico

In silico is an expression used to mean "performed on computer or via computer simulation." The phrase was coined in 1989 as an analogy to the Latin phrases in vivo and in vitro which are commonly used in biology (see also systems biology) and refer to experiments done in living organisms and outside of living organisms, respectively.

Drug discovery with virtual screening
In silico research in medicine is thought to have the potential to speed the rate of discovery while reducing the need for expensive lab work and clinical trials. One way to achieve this is by producing and screening drug candidates more effectively. In 2010, for example, using the protein docking algorithm EADock (see Protein-ligand docking), researchers found potential inhibitors to an enzyme associated with cancer activity in silico. Fifty percent of the molecules were later shown to be active inhibitors in vitro. This approach differs from use of expensive high-throughput screening (HTS) robotic labs to physically test thousands of diverse compounds a day often with an expected hit rate on the order of 1% or less with still fewer expected to be real leads following further testing (see drug discovery).

Cell models
Efforts have been made to establish computer models of cellular behavior. For example, in 2007 researchers developed an in silico model of tuberculosis to aid in drug discovery with a prime benefit cited as being faster than real time simulated growth rates allowing phenomena of interest to be observed in minutes rather than months. More work can be found that focus on modeling a particular cellular process like, for example, the growth cycle of Caulobacter crescentus.

These efforts fall far short of an exact, fully predictive, computer model of a cell's entire behavior. Limitations in the understanding of molecular dynamics and cell biology as well as the absence of available computer processing power force large simplifying assumptions that constrain the usefulness of present in silico models.

Genetics
Digital genetic sequences obtained from DNA sequencing may be stored in sequence databases, be analyzed (see Sequence analysis), be digitally altered and/or be used as templates for creating new actual DNA using artificial gene synthesis.

Other examples
In silico computer-based modeling technologies have also been applied in:
 * Whole cell analysis of prokaryotic and eukaryotic hosts e.g. E. coli, B. subtilis, yeast, CHO- or human cell lines
 * Bioprocess development and optimization e.g. optimization of product yields
 * Analysis, interpretation and visualization of heterologous data sets from various sources e.g. genome, transcriptome or proteome data

History
The expression in silico was first used in public in 1989 in the workshop "Cellular Automata: Theory and Applications" in Los Alamos, New Mexico. Pedro Miramontes, a mathematician from National Autonomous University of Mexico (UNAM) presented the report "DNA and RNA Physicochemical Constraints, Cellular Automata and Molecular Evolution". In his talk, Miramontes used the term "in silico" to characterize biological experiments carried out entirely in a computer. The work was later presented by Miramontes as his PhD dissertation.

In silico has been used in white papers written to support the creation of bacterial genome programs by the Commission of the European Community. The first referenced paper where "in silico" appears was written by a French team in 1991. The first referenced book chapter where "in silico" appears was written by Hans B. Sieburg in 1990 and presented during a Summer School on Complex Systems at the Santa Fe Institute.

The phrase "in silico" originally applied only to computer simulations that modeled natural or laboratory processes (in all the natural sciences), and did not refer to calculations done by computer generically.

In silico versus in silicio
"In silico" was briefly challenged by "in silicio," which is correct Latin for "in silicon". The Latin term for silicon, silicium, was created at the beginning of the 19th century by Berzelius. Silex, meaning flint, is a third declension Latin word in the nominative case, thus with the root silic- for the other cases, from which words like silica are derived in English. The phrase "in silice" means "in flint". However, the adjective in Latin meaning flint-like is silicius,a,um. Many names of elements with the ending -ium come from this adjectival form, e.g. calx (limestone), calcis (of limestone), calcium (limestone-like). In the end, "in silico" was most likely perceived as catchier, possibly through similarity to the words "vivo" and "vitro", and would not have sounded odd given the general disappearance of classical languages in the present curricula. "In silico" is now almost universal; it even occurs in a journal title (In Silico Biology: http://www.bioinfo.de/isb/).

Although the preposition in is Latin and en Greek, in silico is reasonable from the viewpoint of (ancient) Greek case endings; the "-on" ending for certain elements is from Greek. In Greek, "silicon" would take the form "silico" in such a phrase. Latin typically uses the correct Greek forms for Greek words when they are used with Latin prepositions.