Editing Molecular dynamics (section)

== Steered molecular dynamics (SMD) ==

Steered molecular dynamics (SMD) simulations, or force probe simulations, apply forces to a protein in order to manipulate its structure by pulling it along desired degrees of freedom. These experiments can be used to reveal structural changes in a protein at the atomic level. SMD is often used to simulate events such as mechanical unfolding or stretching.<ref name="Nienhaus">{{cite book |title=Protein-ligand interactions: methods and applications |url=https://archive.org/details/proteinligandint00gulr |url-access=registration | vauthors = Nienhaus GU |year=2005 |pages=[https://archive.org/details/proteinligandint00gulr/page/54 54–56] |publisher=Humana Press |isbn=978-1-61737-525-5}}</ref>

There are two typical protocols of SMD: one in which pulling velocity is held constant, and one in which applied force is constant. Typically, part of the studied system (e.g., an atom in a protein) is restrained by a harmonic potential. Forces are then applied to specific atoms at either a constant velocity or a constant force. [[Umbrella sampling]] is used to move the system along the desired reaction coordinate by varying, for example, the forces, distances, and angles manipulated in the simulation. Through umbrella sampling, all of the system's configurations—both high-energy and low-energy—are adequately sampled. Then, each configuration's change in free energy can be calculated as the [[potential of mean force]].<ref name="Leszczyński">{{cite book |title=Computational chemistry: reviews of current trends, Volume 9 | vauthors = Leszczyński J |year=2005 |pages=54–56 | publisher = World Scientific |isbn=978-981-256-742-0}}</ref> A popular method of computing PMF is through the weighted histogram analysis method (WHAM), which analyzes a series of umbrella sampling simulations.<ref>{{cite journal | vauthors = Kumar S, Rosenberg JM, Bouzida D, Swendsen RH, Kollman PA |title=The weighted histogram analysis method for free-energy calculations on biomolecules. I. The method |journal=Journal of Computational Chemistry |date=October 1992 |volume=13 |issue=8 |pages=1011–1021 |doi=10.1002/jcc.540130812 |s2cid=8571486 }}</ref><ref>{{cite journal | vauthors = Bartels C |title=Analyzing biased Monte Carlo and molecular dynamics simulations |journal=Chemical Physics Letters |date=December 2000 |volume=331 |issue=5–6 |pages=446–454 |doi=10.1016/S0009-2614(00)01215-X |bibcode=2000CPL...331..446B }}</ref>

A lot of important applications of SMD are in the field of drug discovery and biomolecular sciences. For e.g. SMD was used to investigate the stability of Alzheimer's protofibrils,<ref>{{cite journal | vauthors = Lemkul JA, Bevan DR | title = Assessing the stability of Alzheimer's amyloid protofibrils using molecular dynamics | journal = The Journal of Physical Chemistry B | volume = 114 | issue = 4 | pages = 1652–1660 | date = February 2010 | pmid = 20055378 | doi = 10.1021/jp9110794 }}</ref> to study the protein ligand interaction in cyclin-dependent kinase 5<ref>{{cite journal | vauthors = Patel JS, Berteotti A, Ronsisvalle S, Rocchia W, Cavalli A | title = Steered molecular dynamics simulations for studying protein-ligand interaction in cyclin-dependent kinase 5 | journal = Journal of Chemical Information and Modeling | volume = 54 | issue = 2 | pages = 470–480 | date = February 2014 | pmid = 24437446 | doi = 10.1021/ci4003574 }}</ref> and even to show the effect of electric field on thrombin (protein) and aptamer (nucleotide) complex<ref>{{cite journal | vauthors = Gosai A, Ma X, Balasubramanian G, Shrotriya P | title = Electrical Stimulus Controlled Binding/Unbinding of Human Thrombin-Aptamer Complex | journal = Scientific Reports | volume = 6 | issue = 1 | pages = 37449 | date = November 2016 | pmid = 27874042 | pmc = 5118750 | doi = 10.1038/srep37449 | bibcode = 2016NatSR...637449G }}</ref> among many other interesting studies.