{"id":307,"date":"2020-02-13T18:47:45","date_gmt":"2020-02-13T18:47:45","guid":{"rendered":"http:\/\/statisticalbiophysicsblog.org\/?p=307"},"modified":"2020-02-13T18:47:46","modified_gmt":"2020-02-13T18:47:46","slug":"lets-fix-md-you-can-help","status":"publish","type":"post","link":"https:\/\/statisticalbiophysicsblog.org\/?p=307","title":{"rendered":"Let\u2019s fix MD \u2013 You can help"},"content":{"rendered":"<p>It\u2019s my view that we must become <em>statistical <\/em>biophysicists.  Why statistical?  Because microscopic behaviors must be repeated zillions of times to create macroscopic effects.  Can you help me shift the thinking in our community?  See below for a collaboration opportunity.<\/p>\n<p><!--more--><\/p>\n<p>Running a single MD simulation of any system really should never be an option.  That\u2019s the realm of <a href=\"https:\/\/statisticalbiophysicsblog.org\/?p=268\">storytelling<\/a> &#8211; not science.  (An exception to the no-single-runs rule is if the simulation is obviously many times longer than key timescales of interest, which is so <a href=\"https:\/\/science.sciencemag.org\/content\/334\/6055\/517.full\">rare<\/a>, we can just ignore the possibility.)  The <a href=\"https:\/\/www.biorxiv.org\/content\/10.1101\/812966v1\">dangers<\/a> of single simulations are simply too great.  Multiple runs provide you with that most beautiful thing: a measure of <a href=\"https:\/\/statisticalbiophysicsblog.org\/?p=180\">variance<\/a>.<\/p>\n<p>I am interested in collaborating on a <a href=\"https:\/\/www.livecomsjournal.org\/post\/130\">Lessons Learned<\/a> article on the limitations of molecular dynamics.  We have a nice data set of multiple runs on an interesting system showing that 500 ns per run isn\u2019t nearly enough sampling to distinguish the behavior of wild-type from a couple of mutants as we\u2019d hoped to do.  Do you have a similar \u2018not worth publishing\u2019 dataset?  Help fight publication bias, and join me in this effort (<a href=\"mailto:zuckermd@ohsu.edu\">zuckermd@ohsu.edu<\/a>).<\/p>\n<p>While we\u2019re worrying about MD, I want to get you worrying that there may be <em>even more<\/em> things to worry about we typically realize.  We all know about force fields, sampling, molecular crowding (potentially in phase-separated regions), and the need for physiological membranes and ions.  So what about ATP?  I\u2019m not talking about ATP\u2019s role in regulating intra-cellular phase separation, but rather ATP simply as a <a href=\"https:\/\/science.sciencemag.org\/content\/356\/6339\/753.abstract\">chemical modulator<\/a> of the environment, like ions.<\/p>\n<p>Why worry about ATP?  For reference, a molecule present at 1M concentration is effectively on a grid with ~12 \u00c5 spacing.  So 1mM corresponds to ~120 \u00c5 spacing.  ATP\u2019s cellular concentration is ~10 mM \u2026 and how big is your protein?  Does your protein have polar or charged groups on its surface?<\/p>\n<p>Worried now?<\/p>\n<p>And what other molecules are present in the cell above mM concentration?  I don\u2019t know.  But surely there are many instances, especially in local regions given the now accepted view of the cell as compartmentalized even outside typical organelles.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>It\u2019s my view that we must become statistical biophysicists. Why statistical? Because microscopic behaviors must be repeated zillions of times to create macroscopic effects. Can you help me shift the thinking in our community? See below for a collaboration opportunity.<\/p>\n","protected":false},"author":6,"featured_media":310,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,18],"tags":[],"class_list":["post-307","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-general-biophysics","category-statistical-uncertainty"],"_links":{"self":[{"href":"https:\/\/statisticalbiophysicsblog.org\/index.php?rest_route=\/wp\/v2\/posts\/307","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/statisticalbiophysicsblog.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/statisticalbiophysicsblog.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/statisticalbiophysicsblog.org\/index.php?rest_route=\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/statisticalbiophysicsblog.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=307"}],"version-history":[{"count":2,"href":"https:\/\/statisticalbiophysicsblog.org\/index.php?rest_route=\/wp\/v2\/posts\/307\/revisions"}],"predecessor-version":[{"id":309,"href":"https:\/\/statisticalbiophysicsblog.org\/index.php?rest_route=\/wp\/v2\/posts\/307\/revisions\/309"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/statisticalbiophysicsblog.org\/index.php?rest_route=\/wp\/v2\/media\/310"}],"wp:attachment":[{"href":"https:\/\/statisticalbiophysicsblog.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=307"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/statisticalbiophysicsblog.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=307"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/statisticalbiophysicsblog.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=307"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}