Tutorial:The opioid receptor, a molecular switch: Difference between revisions

Line 74:

In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> set refreshing false; load $oxycodone; background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality2.JPG"; select _C; color mediumpurple; hide _H; moveto 1.0 { -977 204 68 164.66} 5.0 -34.67 36.52 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { -1000 21 -14 66.69} 46.78 -22.06 -16.47 {-0.81575 0.02959999999999985 -0.13314999999999988} 7.056706882620149 {0 0 0} 0 0 0 3.0 0.0 0.0; set zshade on; set zshadepower 1; set spinY 0; set spinX 90; spin on;</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>set refreshing false; load $heroin; background image "http://proteopedia.org/wiki/images/e/e6/OpioidFatality3.JPG"; select _C; color orange; hide _H; set zshade on; set zshadepower 1; moveto 1.0 { 970 216 -113 30.11} 5.0 -8.1 36.32 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { 997 68 23 122.37} 42.42 3.87 -19.17 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>set refreshing false; load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1; background image "http://proteopedia.org/wiki/images/5/51/OpioidFatality4.JPG"; moveto 1.0 { 802 6 -597 24.36} 5.1 32.85 34.38 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0;; set refreshing true; moveto 1.0 { -997 -67 -31 130.64} 55.02 -9.39 -19.75 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>fentanyl</text></jmolLink></jmol>.

To explore how naloxone reverses an overdose, let's look at the situation during an overdose. The opioid receptor binding pocket is occupied by <scene name='83/830406/Competition/1'>the opioid agonist</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]

To explore how naloxone reverses an overdose, let's look at the situation during an overdose. The opioid receptor binding pocket is occupied by <scene name='83/830406/Competition/2'>the opioid agonist</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]

ago1 = [ {-28.15225471470447 -16.732834272032683 -19.877771911210033},{-27.699108229899412 -15.289706379445466 -19.75851945234414},{-26.68480597889424 -16.41202791313621 -19.553508919395476},{-26.088235349655854 -16.524656204830176 -18.11797335653394},{-26.09670821218129 -17.86095364239696 -17.47014979339886},{-25.422698574661922 -17.721641670729095 -16.199593937451922},{-25.353924216489737 -19.013933850033702 -15.411718940408532},{-26.803804141690954 -19.477321003972328 -15.178642669494419},{-27.445395730810528 -18.494213544008844 -14.383647100365163},{-26.818636191572715 -20.537559246853444 -14.291420105179995},{-26.27682344603074 -19.760003263026004 -13.14885472815232},{-27.207435082797755 -18.77153045507903 -13.06873301160048},{-27.480530055558386 -17.69570033702936 -12.353598273980962},{-27.244161412119684 -17.860947196252614 -11.025351181036363},{-28.364696788636234 -16.68825679789819 -12.736096252513157},{-28.711030406563342 -16.531400987159827 -14.066644365033392},{-28.151812675248582 -17.470874662546446 -14.908529596070698},{-28.472248612776976 -17.533960092984973 -16.285274684460944},{-27.462151991406987 -18.37594262285864 -17.143213047564316},{-27.524423894082027 -19.730606208555294 -16.490990861706834},{-26.83847374040866 -20.703170645740975 -17.280056639824984},{-28.958513651925706 -20.17265541019972 -16.19507859468611},{-28.992617235384415 -21.42435546162589 -15.35837319440775},{-28.25116136928705 -21.038824300654305 -14.024697475745336},{-28.19935710109749 -22.168541971976264 -13.079524845534207},{-29.32189117303061 -22.73375369850398 -12.596195804874707},{-30.46083909789644 -22.348636080546093 -12.857454383264495},{-29.114561027297814 -23.897271044635005 -11.626157869573909},{-30.33443496035501 -24.825982830819825 -11.746855863131952},{-30.532177135749723 -25.36260046177555 -13.177744241104742},{-31.66401160803267 -25.612658051750717 -13.595648451478052},{-29.401879118904926 -25.52914420794582 -13.91816207836175},{-29.753259103332216 -26.02310392303815 -15.217442227678971} ]

ago2 = [ {-34.26386300135435 -32.998407428317655 -22.075040189835274},{-33.767972005394476 -31.785329790003857 -22.839707283117654},{-32.81949446748223 -32.50861138609696 -21.886975372856973},{-32.35656815162927 -31.686026101800934 -20.646654174074015},{-32.47337487759003 -32.32592942722871 -19.311619371952094},{-31.909159051353825 -31.40751839168098 -18.34923136745037},{-31.95973567715373 -31.923733461475216 -16.925693518764934},{-33.4412224403542 -32.17676717971283 -16.590469850303663},{-34.11221904893955 -30.92900307598431 -16.645299520315255},{-33.57487543154809 -32.45184072304114 -15.2421522231454},{-33.10647751293254 -31.118043986270415 -14.789162538035006},{-34.00192443298045 -30.31933222157224 -15.429295594757907},{-34.295534080630205 -29.039691289330616 -15.569728708156578},{-34.183700632061864 -28.334200342225728 -14.413358177861756},{-35.10323791540406 -28.51359767071855 -16.576623945878502},{-35.32464590971701 -29.22984459328295 -17.73975671816693},{-34.72983387573878 -30.474848641138685 -17.756175154681134},{-34.929828129067715 -31.39106893129418 -18.815716885120633},{-33.88107103855785 -32.55859275560962 -18.863515261255557},{-34.05251987303332 -33.21145171171779 -17.518611740334293},{-33.33748856327233 -34.44616521213911 -17.461631059934426},{-35.52301088127194 -33.4082201330449 -17.146424444664728},{-35.67873675808378 -33.864851905275984 -15.719809964197012},{-35.04350716039007 -32.713035578674216 -14.855585162431051},{-35.118606741265054 -33.00455404223835 -13.412784400595367},{-36.30023295955805 -33.172773248311614 -12.789393849695967},{-37.396098399213365 -33.06357624654339 -13.337963765908942},{-36.22401589209895 -33.471269879876516 -11.291788187456293},{-37.463222185329336 -34.30270376192125 -10.919966371788991},{-37.55448205900263 -35.619509969151274 -11.715073313060199},{-38.6538216409946 -36.10401782266501 -11.98880059220686},{-36.37053195093635 -36.183083352673265 -12.081373985999198},{-36.624684431568774 -37.388328417582294 -12.815120434100198} ]

@@ Line 74: / Line 74: @@
 In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> set refreshing false; load $oxycodone; background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality2.JPG";  select _C; color mediumpurple; hide _H; moveto 1.0 { -977 204 68 164.66} 5.0 -34.67 36.52 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { -1000 21 -14 66.69} 46.78 -22.06 -16.47 {-0.81575 0.02959999999999985 -0.13314999999999988} 7.056706882620149 {0 0 0} 0 0 0 3.0 0.0 0.0; set zshade on; set zshadepower 1; set spinY 0; set spinX 90; spin on;</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>set refreshing false; load $heroin; background image "http://proteopedia.org/wiki/images/e/e6/OpioidFatality3.JPG"; select _C; color orange; hide _H; set zshade on; set zshadepower 1; moveto 1.0 { 970 216 -113 30.11} 5.0 -8.1 36.32 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { 997 68 23 122.37} 42.42 3.87 -19.17 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>set refreshing false; load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1; background image "http://proteopedia.org/wiki/images/5/51/OpioidFatality4.JPG"; moveto 1.0 { 802 6 -597 24.36} 5.1 32.85 34.38 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0;; set refreshing true; moveto 1.0 { -997 -67 -31 130.64} 55.02 -9.39 -19.75 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>fentanyl</text></jmolLink></jmol>.
-To explore how naloxone reverses an overdose, let's look at the situation during an overdose. The opioid receptor binding pocket is occupied by <scene name='83/830406/Competition/1'>the opioid agonist</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]
+To explore how naloxone reverses an overdose, let's look at the situation during an overdose. The opioid receptor binding pocket is occupied by <scene name='83/830406/Competition/2'>the opioid agonist</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]
 ago1 = [ {-28.15225471470447 -16.732834272032683 -19.877771911210033},{-27.699108229899412 -15.289706379445466 -19.75851945234414},{-26.68480597889424 -16.41202791313621 -19.553508919395476},{-26.088235349655854 -16.524656204830176 -18.11797335653394},{-26.09670821218129 -17.86095364239696 -17.47014979339886},{-25.422698574661922 -17.721641670729095 -16.199593937451922},{-25.353924216489737 -19.013933850033702 -15.411718940408532},{-26.803804141690954 -19.477321003972328 -15.178642669494419},{-27.445395730810528 -18.494213544008844 -14.383647100365163},{-26.818636191572715 -20.537559246853444 -14.291420105179995},{-26.27682344603074 -19.760003263026004 -13.14885472815232},{-27.207435082797755 -18.77153045507903 -13.06873301160048},{-27.480530055558386 -17.69570033702936 -12.353598273980962},{-27.244161412119684 -17.860947196252614 -11.025351181036363},{-28.364696788636234 -16.68825679789819 -12.736096252513157},{-28.711030406563342 -16.531400987159827 -14.066644365033392},{-28.151812675248582 -17.470874662546446 -14.908529596070698},{-28.472248612776976 -17.533960092984973 -16.285274684460944},{-27.462151991406987 -18.37594262285864 -17.143213047564316},{-27.524423894082027 -19.730606208555294 -16.490990861706834},{-26.83847374040866 -20.703170645740975 -17.280056639824984},{-28.958513651925706 -20.17265541019972 -16.19507859468611},{-28.992617235384415 -21.42435546162589 -15.35837319440775},{-28.25116136928705 -21.038824300654305 -14.024697475745336},{-28.19935710109749 -22.168541971976264 -13.079524845534207},{-29.32189117303061 -22.73375369850398 -12.596195804874707},{-30.46083909789644 -22.348636080546093 -12.857454383264495},{-29.114561027297814 -23.897271044635005 -11.626157869573909},{-30.33443496035501 -24.825982830819825 -11.746855863131952},{-30.532177135749723 -25.36260046177555 -13.177744241104742},{-31.66401160803267 -25.612658051750717 -13.595648451478052},{-29.401879118904926 -25.52914420794582 -13.91816207836175},{-29.753259103332216 -26.02310392303815 -15.217442227678971} ]
 ago2 = [ {-34.26386300135435 -32.998407428317655 -22.075040189835274},{-33.767972005394476 -31.785329790003857 -22.839707283117654},{-32.81949446748223 -32.50861138609696 -21.886975372856973},{-32.35656815162927 -31.686026101800934 -20.646654174074015},{-32.47337487759003 -32.32592942722871 -19.311619371952094},{-31.909159051353825 -31.40751839168098 -18.34923136745037},{-31.95973567715373 -31.923733461475216 -16.925693518764934},{-33.4412224403542 -32.17676717971283 -16.590469850303663},{-34.11221904893955 -30.92900307598431 -16.645299520315255},{-33.57487543154809 -32.45184072304114 -15.2421522231454},{-33.10647751293254 -31.118043986270415 -14.789162538035006},{-34.00192443298045 -30.31933222157224 -15.429295594757907},{-34.295534080630205 -29.039691289330616 -15.569728708156578},{-34.183700632061864 -28.334200342225728 -14.413358177861756},{-35.10323791540406 -28.51359767071855 -16.576623945878502},{-35.32464590971701 -29.22984459328295 -17.73975671816693},{-34.72983387573878 -30.474848641138685 -17.756175154681134},{-34.929828129067715 -31.39106893129418 -18.815716885120633},{-33.88107103855785 -32.55859275560962 -18.863515261255557},{-34.05251987303332 -33.21145171171779 -17.518611740334293},{-33.33748856327233 -34.44616521213911 -17.461631059934426},{-35.52301088127194 -33.4082201330449 -17.146424444664728},{-35.67873675808378 -33.864851905275984 -15.719809964197012},{-35.04350716039007 -32.713035578674216 -14.855585162431051},{-35.118606741265054 -33.00455404223835 -13.412784400595367},{-36.30023295955805 -33.172773248311614 -12.789393849695967},{-37.396098399213365 -33.06357624654339 -13.337963765908942},{-36.22401589209895 -33.471269879876516 -11.291788187456293},{-37.463222185329336 -34.30270376192125 -10.919966371788991},{-37.55448205900263 -35.619509969151274 -11.715073313060199},{-38.6538216409946 -36.10401782266501 -11.98880059220686},{-36.37053195093635 -36.183083352673265 -12.081373985999198},{-36.624684431568774 -37.388328417582294 -12.815120434100198} ]