In silico

{{Short description|Latin phrase referring to computer simulations}} {{italic title}} {{Other uses}} [[File:Forest of synthetic pyramidal dendrites grown using Cajal's laws of neuronal branching.png|thumb|A forest of synthetic pyramidal dendrites generated ''in silico'' using Cajal's laws of neuronal branching]]

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' (correct {{langx|la|in silicio}}), referring to silicon in computer chips. It was coined in 1987 as an allusion to the Latin phrases {{lang|la|in vivo}}, {{lang|la|in vitro}}, and {{lang|la|in situ}}, which are commonly used in biology (especially systems biology). The latter phrases refer, respectively, to experiments done in living organisms, outside living organisms, and where they are found in nature.

==History== The earliest known use of the phrase was by Christopher Langton to describe artificial life, in the announcement of a workshop on that subject at the Center for Nonlinear Studies at the Los Alamos National Laboratory in 1987.<ref>{{Cite web|url=https://groups.google.com/forum/#!topic/news.announce.conferences/d2oq9H2venM|title=Google Groups|website=groups.google.com|access-date=2020-01-05}}</ref><ref>{{Cite book|url=https://books.google.com/books?id=-uC54_DD0tMC&pg=PA273|title=Ultimate Computing: Biomolecular Consciousness and NanoTechnology|last=Hameroff|first=S. R.|date=2014-04-11|publisher=Elsevier|isbn=978-0-444-60009-7|language=en}}</ref> The expression ''in silico'' was first used to characterize biological experiments carried out entirely in a computer in 1989, in the workshop "Cellular Automata: Theory and Applications" in Los Alamos, New Mexico, by Pedro Miramontes, a mathematician from National Autonomous University of Mexico (UNAM), presenting the report "DNA and RNA Physicochemical Constraints, Cellular Automata and Molecular Evolution". The work was later presented by Miramontes as his dissertation.<ref name=Miramontes>Miramontes P. (1992) ''Un modelo de autómata celular para la evolución de los ácidos nucleicos'' [A cellular automaton model for the evolution of nucleic acids]. PhD Thesis. UNAM.</ref>

''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.<ref name=Danchin>{{Citation| last1 = Danchin | first1 = A | last2 = Médigue | first2 = C | last3 = Gascuel | first3 = O | last4 = Soldano | first4 = H | last5 = Hénaut | first5 = A | title = From data banks to data bases | journal = Research in Microbiology | volume = 142 | issue = 7–8 | pages = 913–6 | year = 1991 | pmid = 1784830 | doi = 10.1016/0923-2508(91)90073-J | citeseerx = 10.1.1.637.3244 }}</ref> 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.<ref name=Sieburg>{{Citation| last1 = Sieburg | first1 = H.B. | year = 1990 | title = Physiological Studies ''in silico'' | journal = Studies in the Sciences of Complexity | volume = 12 | pages = 321–342 }}</ref>

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.

==Drug discovery with virtual screening== {{Main|virtual screening}}

''In silico'' study 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''.<ref>{{Citation| last1 = Röhrig | first1 = Ute F. | last2 = Awad | first2 = Loay | last3 = Grosdidier | first3 = AuréLien | last4 = Larrieu | first4 = Pierre | last5 = Stroobant | first5 = Vincent | last6 = Colau | first6 = Didier | last7 = Cerundolo | first7 = Vincenzo | last8 = Simpson | first8 = Andrew J. G. | last9 = Vogel | first9 = Pierre | last10 = Van Den Eynde | first10 = Benoît J. | last11 = Zoete | first11 = Vincent | last12 = Michielin | first12 = Olivier | title = Rational Design of Indoleamine 2,3-Dioxygenase Inhibitors | journal = Journal of Medicinal Chemistry | volume = 53 | pages = 1172–89 | year = 2010 | doi = 10.1021/jm9014718 | issue = 3 | pmid = 20055453 | display-authors = 8 }}</ref><ref>Ludwig Institute for Cancer Research (2010, February 4). [https://www.sciencedaily.com/releases/2010/01/100129151756.htm New computational tool for cancer treatment]. ''ScienceDaily''. Retrieved February 12, 2010.</ref> 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).

As an example, the technique was utilized for a drug repurposing study in order to search for potential cures for COVID-19 (SARS-CoV-2).<ref>{{Cite journal|doi=10.36877/pddbs.a0000065|title=Computational screening and identifying binding interaction of anti-viral and anti-malarial drugs: Toward the potential cure for SARS-CoV-2|year=2020|last1=Lee|first1=Vannajan Sanghiran|last2=Chong|first2=Wei Lim|last3=Sukumaran|first3=Sri Devi|last4=Nimmanpipug|first4=Pivarat|last5=Letchumanan|first5=Vengadesh|last6=Goh|first6=Bey Hing|last7=Lee|first7=Learn-Han|last8=Md. Zain|first8=Sharifuddin|last9=Abd Rahman|first9=Noorsaadah|journal=Progress in Drug Discovery & Biomedical Science|volume=3|doi-access=free}}</ref>

==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 the prime benefit of its being faster than real time simulated growth rates, allowing phenomena of interest to be observed in minutes rather than months.<ref>University Of Surrey. June 25, 2007. [https://www.sciencedaily.com/releases/2007/06/070624135714.htm In Silico Cell For TB Drug Discovery]. ''ScienceDaily''. Retrieved February 12, 2010.</ref> More work can be found that focus on modeling a particular cellular process such as the growth cycle of ''Caulobacter crescentus''.<ref>{{cite journal | last1 = Li | first1 = S | last2 = Brazhnik | first2 = P | last3 = Sobral | first3 = B | last4 = Tyson | first4 = JJ | author4-link = John J. Tyson | year = 2009 | title = Temporal Controls of the Asymmetric Cell Division Cycle in Caulobacter crescentus | journal = PLOS Comput Biol | volume = 5 | issue = 8| article-number = e1000463 | doi = 10.1371/journal.pcbi.1000463 | pmid = 19680425 | pmc = 2714070 | bibcode = 2009PLSCB...5E0463L | doi-access = free }}</ref>

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 cell models.

==Genetics== Digital genetic sequences obtained from DNA sequencing may be stored in sequence databases, be analyzed (see Sequence analysis), be digitally altered 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 * Discovery of potential cure for COVID-19.<ref>{{Cite journal|doi=10.36877/pddbs.a0000065|title=Computational screening and identifying binding interaction of anti-viral and anti-malarial drugs: Toward the potential cure for SARS-CoV-2|year=2020|last1=Lee|first1=Vannajan Sanghiran|last2=Chong|first2=Wei Lim|last3=Sukumaran|first3=Sri Devi|last4=Nimmanpipug|first4=Pivarat|last5=Letchumanan|first5=Vengadesh|last6=Goh|first6=Bey Hing|last7=Lee|first7=Learn-Han|last8=Md. Zain|first8=Sharifuddin|last9=Abd Rahman|first9=Noorsaadah|journal=Progress in Drug Discovery & Biomedical Science|volume=3|doi-access=free}}</ref> * Bioprocess development and optimization e.g. optimization of product yields * Simulation of oncological clinical trials exploiting grid computing infrastructures, such as the European Grid Infrastructure, for improving the performance and effectiveness of the simulations.<ref>{{cite journal | author=Athanaileas, Theodoros| title=Exploiting grid technologies for the simulation of clinical trials: the paradigm of in silico radiation oncology | journal=SIMULATION: Transactions of the Society for Modeling and Simulation International | volume=87 | number=10 | pages=893–910 | year=2011 | doi=10.1177/0037549710375437| s2cid=206429690 |display-authors=etal}}</ref> * Analysis, interpretation and visualization of heterologous data sets from various sources e.g. genome, transcriptome or proteome data * Validation of taxonomic assignment steps in herbivore metagenomics study.<ref>{{cite journal |last1=Chua |first1=Physilia Y. S. |last2=Crampton-Platt |first2=Alex |last3=Lammers |first3=Youri |last4=Alsos |first4=Inger G. |last5=Boessenkool |first5=Sanne |last6=Bohmann |first6=Kristine |title=Metagenomics: A viable tool for reconstructing herbivore diet |journal=Molecular Ecology Resources |year=2021 |volume=21 |issue=7 |pages=2249–2263 |doi=10.1111/1755-0998.13425 |pmc=8518049|pmid=33971086 |doi-access=free }}</ref> * Protein design. One example is RosettaDesign, a software package under development and free for academic use.<ref>{{Citation |title=RosettaDesign server for protein design |journal=Nucleic Acids Research |volume=34 |issue=Web Server issue |pages=W235–8 |date=July 2006 |pmc=1538902 |doi=10.1093/nar/gkl163 |pmid=16845000 |last1=Liu |first1=Y |last2=Kuhlman |first2=B}}</ref><ref>{{Citation |doi=10.1016/S0022-2836(03)00888-X |title=A Large Scale Test of Computational Protein Design: Folding and Stability of Nine Completely Redesigned Globular Proteins |year=2003 |last1=Dantas |first1=Gautam |last2=Kuhlman |first2=Brian |last3=Callender |first3=David |last4=Wong |first4=Michelle |last5=Baker |first5=David |journal=Journal of Molecular Biology |volume=332 |pages=449–60 |postscript=. |pmid=12948494 |issue=2|citeseerx=10.1.1.66.8110 }}</ref><ref>{{Citation |doi=10.1016/j.str.2006.02.011 |title=High-Resolution Structural Validation of the Computational Redesign of Human U1A Protein |year=2006 |last1=Dobson |first1=N |last2=Dantas |first2=G |last3=Baker |first3=D |last4=Varani |first4=G |journal=Structure |volume=14 |pages=847–56 |postscript=. |pmid=16698546 |issue=5|doi-access=free }}</ref><ref>{{Citation |doi=10.1016/j.jmb.2006.11.080 |title=High-resolution Structural and Thermodynamic Analysis of Extreme Stabilization of Human Procarboxypeptidase by Computational Protein Design |year=2007 |last1=Dantas |first1=G |last2=Corrent |first2=C |last3=Reichow |first3=S |last4=Havranek |first4=J |last5=Eletr |first5=Z |last6=Isern |first6=N |last7=Kuhlman |first7=B |last8=Varani |first8=G |last9=Merritt |first9=E |last10=Baker |first10=David |journal=Journal of Molecular Biology |volume=366 |pages=1209–21 |postscript=. |pmid=17196978 |issue=4|display-authors=8 |pmc=3764424 }}</ref>

==References== {{Reflist}}

==External links== {{wiktionary}} * [http://www.worldwidewords.org/weirdwords/ww-ins1.htm World Wide Words: ''In silico''] * [http://www.cadaster.eu CADASTER] {{Webarchive|url=https://web.archive.org/web/20120330200549/http://www.cadaster.eu/ |date=2012-03-30 }} Seventh Framework Programme project aimed to develop in silico computational methods to minimize experimental tests for REACH Registration, Evaluation, Authorisation and Restriction of Chemicals * [http://www.insilicobiologyjournal.com/ In Silico Biology. Journal of Biological Systems Modeling and Simulation] {{Webarchive|url=https://web.archive.org/web/20201021191307/https://www.insilicobiologyjournal.com/ |date=2020-10-21 }} * [http://www.in-silico-pharmacology.com/ In Silico Pharmacology] {{Research methods in biology}} {{Portal bar|Science|Physics|Biology|Chemistry|Computer programming|Astronomy|Science}}

{{DEFAULTSORT:In Silico}} Category:Pharmaceutical industry Category:Latin biological phrases Category:Alternatives to animal testing Category:Animal test conditions