Editing Protein structure prediction (section)

====Energy- and fragment-based methods====
''Ab initio''- or ''de novo''- protein modelling methods seek to build three-dimensional protein models "from scratch", i.e., based on physical principles rather than (directly) on previously solved structures. There are many possible procedures that either attempt to mimic [[protein folding]] or apply some [[stochastic]] method to search possible solutions (i.e., [[global optimization]] of a suitable energy function). These procedures tend to require vast computational resources, and have thus only been carried out for tiny proteins. To predict protein structure ''de novo'' for larger proteins will require better algorithms and larger computational resources like those afforded by either powerful supercomputers (such as [[Blue Gene]] or [[MDGRAPE-3]]) or distributed computing (such as [[Folding@home]], the [[Human Proteome Folding Project]] and [[Rosetta@Home]]). Although these computational barriers are vast, the potential benefits of structural genomics (by predicted or experimental methods) make ''ab initio'' structure prediction an active research field.<ref name="zhang2008">{{cite journal |vauthors=Zhang Y |title=Progress and challenges in protein structure prediction |journal=Current Opinion in Structural Biology |volume=18 |issue=3 |pages=342–8 |date=June 2008 |pmid=18436442 |pmc=2680823 |doi=10.1016/j.sbi.2008.02.004}}</ref>

As of 2009, a 50-residue protein could be simulated atom-by-atom on a supercomputer for 1 millisecond.<ref name="ShawBowers2009">{{cite conference| vauthors=Shaw DE, Dror RO, Salmon JK, Grossman JP, Mackenzie KM, Bank JA, Young C, Deneroff MM, Batson B, Bowers KJ, Chow E |conference=Proceedings of the Conference on High Performance Computing Networking, Storage and Analysis – SC '09 |year=2009|pages=1|doi=10.1145/1654059.1654126|title=Millisecond-scale molecular dynamics simulations on Anton|isbn=9781605587448|doi-access=}}</ref> As of 2012, comparable stable-state sampling could be done on a standard desktop with a new graphics card and more sophisticated algorithms.<ref name="PierceSalomon-Ferrer2012">{{cite journal |vauthors=Pierce LC, Salomon-Ferrer R, de Oliveira CA, McCammon JA, Walker RC |title=Routine Access to Millisecond Time Scale Events with Accelerated Molecular Dynamics |journal=Journal of Chemical Theory and Computation |volume=8 |issue=9 |pages=2997–3002 |date=September 2012 |pmid=22984356 |pmc=3438784 |doi=10.1021/ct300284c}}</ref> A much larger simulation timescales can be achieved using [[coarse-grained modeling]].<ref>{{cite journal |vauthors=Kmiecik S, Gront D, Kolinski M, Wieteska L, Dawid AE, Kolinski A |title=Coarse-Grained Protein Models and Their Applications |journal=Chemical Reviews |volume=116 |issue=14 |pages=7898–936 |date=July 2016 |pmid=27333362 |doi=10.1021/acs.chemrev.6b00163 |doi-access=free}}</ref><ref name="denovo2018">{{cite journal |vauthors=Cheung NJ, Yu W |title=De novo protein structure prediction using ultra-fast molecular dynamics simulation |journal=PLOS ONE |volume=13| issue=11 |pages=e0205819 |date=November 2018 |pmid=30458007 |pmc=6245515 |doi=10.1371/journal.pone.0205819 |bibcode=2018PLoSO..1305819C |doi-access=free}}</ref>