[{"data":1,"prerenderedAt":1067},["ShallowReactive",2],{"mdc-if5uby-key":3},{"data":4,"body":5},{},{"type":6,"children":7},"root",[8,17,45,49,55,60,69,80,87,98,107,112,137,142,234,239,251,276,279,285,296,301,306,314,319,327,332,340,345,363,371,382,388,406,424,427,433,444,449,457,468,474,492,510,513,519,524,539,550,556,561,593,598,625,637,649,652,658,670,676,681,686,694,700,705,718,724,735,738,744,756,764,767,773,784,789,825,830,841,844,850,862,866,874,878,892,895,901,912,917,936,947,950,956,962,967,970,976,981,984,990,995,998,1004,1009,1012,1018,1023,1041,1044,1054],{"type":9,"tag":10,"props":11,"children":13},"element","h1",{"id":12},"lecture-summary-proteinligand-binding-strength-day-6",[14],{"type":15,"value":16},"text","📚 Lecture Summary — Protein–Ligand Binding Strength (Day 6)",{"type":9,"tag":18,"props":19,"children":20},"p",{},[21,23,29,31,36,38,43],{"type":15,"value":22},"This lecture focuses on ",{"type":9,"tag":24,"props":25,"children":26},"strong",{},[27],{"type":15,"value":28},"how proteins bind ligands",{"type":15,"value":30},", how to ",{"type":9,"tag":24,"props":32,"children":33},{},[34],{"type":15,"value":35},"interpret the dissociation constant (KD)",{"type":15,"value":37},", and why ",{"type":9,"tag":24,"props":39,"children":40},{},[41],{"type":15,"value":42},"ligands eventually dissociate even when binding occurs",{"type":15,"value":44},".",{"type":9,"tag":46,"props":47,"children":48},"hr",{},[],{"type":9,"tag":10,"props":50,"children":52},{"id":51},"_1-what-determines-strong-vs-weak-binding",[53],{"type":15,"value":54},"🧬 1. What Determines Strong vs Weak Binding?",{"type":9,"tag":18,"props":56,"children":57},{},[58],{"type":15,"value":59},"One of the key questions in protein biophysics is:",{"type":9,"tag":61,"props":62,"children":63},"blockquote",{},[64],{"type":9,"tag":18,"props":65,"children":66},{},[67],{"type":15,"value":68},"When is a protein–ligand interaction considered strong or weak?",{"type":9,"tag":18,"props":70,"children":71},{},[72,74,79],{"type":15,"value":73},"The answer depends on the ",{"type":9,"tag":24,"props":75,"children":76},{},[77],{"type":15,"value":78},"dissociation constant (KD)",{"type":15,"value":44},{"type":9,"tag":81,"props":82,"children":84},"h3",{"id":83},"dissociation-constant-kd",[85],{"type":15,"value":86},"🔑 Dissociation Constant (KD)",{"type":9,"tag":18,"props":88,"children":89},{},[90,92,97],{"type":15,"value":91},"KD describes the ",{"type":9,"tag":24,"props":93,"children":94},{},[95],{"type":15,"value":96},"affinity between a protein and a ligand",{"type":15,"value":44},{"type":9,"tag":18,"props":99,"children":100},{},[101],{"type":9,"tag":102,"props":103,"children":104},"span",{},[105],{"type":15,"value":106},"\nK_D = \frac{k_}{k_}\n",{"type":9,"tag":18,"props":108,"children":109},{},[110],{"type":15,"value":111},"Where:",{"type":9,"tag":113,"props":114,"children":115},"ul",{},[116,127],{"type":9,"tag":117,"props":118,"children":119},"li",{},[120,125],{"type":9,"tag":24,"props":121,"children":122},{},[123],{"type":15,"value":124},"k_on",{"type":15,"value":126}," = association rate constant (binding rate)",{"type":9,"tag":117,"props":128,"children":129},{},[130,135],{"type":9,"tag":24,"props":131,"children":132},{},[133],{"type":15,"value":134},"k_off",{"type":15,"value":136}," = dissociation rate constant (unbinding rate)",{"type":9,"tag":18,"props":138,"children":139},{},[140],{"type":15,"value":141},"Interpretation:",{"type":9,"tag":143,"props":144,"children":145},"table",{},[146,165],{"type":9,"tag":147,"props":148,"children":149},"thead",{},[150],{"type":9,"tag":151,"props":152,"children":153},"tr",{},[154,160],{"type":9,"tag":155,"props":156,"children":157},"th",{},[158],{"type":15,"value":159},"KD Range",{"type":9,"tag":155,"props":161,"children":162},{},[163],{"type":15,"value":164},"Binding Strength",{"type":9,"tag":166,"props":167,"children":168},"tbody",{},[169,186,202,218],{"type":9,"tag":151,"props":170,"children":171},{},[172,181],{"type":9,"tag":173,"props":174,"children":175},"td",{},[176],{"type":9,"tag":24,"props":177,"children":178},{},[179],{"type":15,"value":180},"mM (10⁻³ M)",{"type":9,"tag":173,"props":182,"children":183},{},[184],{"type":15,"value":185},"Weak binding",{"type":9,"tag":151,"props":187,"children":188},{},[189,197],{"type":9,"tag":173,"props":190,"children":191},{},[192],{"type":9,"tag":24,"props":193,"children":194},{},[195],{"type":15,"value":196},"µM (10⁻⁶ M)",{"type":9,"tag":173,"props":198,"children":199},{},[200],{"type":15,"value":201},"Moderate binding",{"type":9,"tag":151,"props":203,"children":204},{},[205,213],{"type":9,"tag":173,"props":206,"children":207},{},[208],{"type":9,"tag":24,"props":209,"children":210},{},[211],{"type":15,"value":212},"sub-µM (\u003C10⁻⁶ M)",{"type":9,"tag":173,"props":214,"children":215},{},[216],{"type":15,"value":217},"Strong binding",{"type":9,"tag":151,"props":219,"children":220},{},[221,229],{"type":9,"tag":173,"props":222,"children":223},{},[224],{"type":9,"tag":24,"props":225,"children":226},{},[227],{"type":15,"value":228},"nM or sub-nM",{"type":9,"tag":173,"props":230,"children":231},{},[232],{"type":15,"value":233},"Very strong binding",{"type":9,"tag":18,"props":235,"children":236},{},[237],{"type":15,"value":238},"Important note:",{"type":9,"tag":18,"props":240,"children":241},{},[242,244,249],{"type":15,"value":243},"⚠️ These boundaries are ",{"type":9,"tag":24,"props":245,"children":246},{},[247],{"type":15,"value":248},"not strict rules",{"type":15,"value":250},". They are approximate classifications used in biochemistry.",{"type":9,"tag":18,"props":252,"children":253},{},[254,256,261,263,268,270,275],{"type":15,"value":255},"In the lecture example, a ",{"type":9,"tag":24,"props":257,"children":258},{},[259],{"type":15,"value":260},"millimolar KD",{"type":15,"value":262}," was measured for an ",{"type":9,"tag":24,"props":264,"children":265},{},[266],{"type":15,"value":267},"alginate oligomer binding to a protein",{"type":15,"value":269},", which indicates ",{"type":9,"tag":24,"props":271,"children":272},{},[273],{"type":15,"value":274},"weak binding",{"type":15,"value":44},{"type":9,"tag":46,"props":277,"children":278},{},[],{"type":9,"tag":10,"props":280,"children":282},{"id":281},"️-2-how-kd-relates-to-dissociation-rates",[283],{"type":15,"value":284},"⏱️ 2. How KD Relates to Dissociation Rates",{"type":9,"tag":18,"props":286,"children":287},{},[288,290,295],{"type":15,"value":289},"Even when binding occurs, ligands may ",{"type":9,"tag":24,"props":291,"children":292},{},[293],{"type":15,"value":294},"leave the protein quickly",{"type":15,"value":44},{"type":9,"tag":18,"props":297,"children":298},{},[299],{"type":15,"value":300},"Example given in the lecture:",{"type":9,"tag":18,"props":302,"children":303},{},[304],{"type":15,"value":305},"If:",{"type":9,"tag":18,"props":307,"children":308},{},[309],{"type":9,"tag":102,"props":310,"children":311},{},[312],{"type":15,"value":313},"\nk_ = 10^7 ; M^{-1}s^{-1}\n",{"type":9,"tag":18,"props":315,"children":316},{},[317],{"type":15,"value":318},"and",{"type":9,"tag":18,"props":320,"children":321},{},[322],{"type":9,"tag":102,"props":323,"children":324},{},[325],{"type":15,"value":326},"\nK_D = 1 mu M\n",{"type":9,"tag":18,"props":328,"children":329},{},[330],{"type":15,"value":331},"Then:",{"type":9,"tag":18,"props":333,"children":334},{},[335],{"type":9,"tag":102,"props":336,"children":337},{},[338],{"type":15,"value":339},"\nk_ = 10 s^{-1}\n",{"type":9,"tag":18,"props":341,"children":342},{},[343],{"type":15,"value":344},"Meaning:",{"type":9,"tag":113,"props":346,"children":347},{},[348,358],{"type":9,"tag":117,"props":349,"children":350},{},[351,353],{"type":15,"value":352},"The ligand ",{"type":9,"tag":24,"props":354,"children":355},{},[356],{"type":15,"value":357},"unbinds ~10 times per second",{"type":9,"tag":117,"props":359,"children":360},{},[361],{"type":15,"value":362},"Average lifetime of the complex:",{"type":9,"tag":18,"props":364,"children":365},{},[366],{"type":9,"tag":102,"props":367,"children":368},{},[369],{"type":15,"value":370},"\n\frac{1}{k_} = 0.1 s\n",{"type":9,"tag":18,"props":372,"children":373},{},[374,376,381],{"type":15,"value":375},"So the ligand stays bound only about ",{"type":9,"tag":24,"props":377,"children":378},{},[379],{"type":15,"value":380},"100 milliseconds",{"type":15,"value":44},{"type":9,"tag":81,"props":383,"children":385},{"id":384},"interpretation",[386],{"type":15,"value":387},"🧠 Interpretation",{"type":9,"tag":18,"props":389,"children":390},{},[391,393,398,400,405],{"type":15,"value":392},"Even though binding occurs, the ligand ",{"type":9,"tag":24,"props":394,"children":395},{},[396],{"type":15,"value":397},"dissociates frequently",{"type":15,"value":399},", meaning the interaction is ",{"type":9,"tag":24,"props":401,"children":402},{},[403],{"type":15,"value":404},"not very stable",{"type":15,"value":44},{"type":9,"tag":18,"props":407,"children":408},{},[409,411,416,418,423],{"type":15,"value":410},"A ",{"type":9,"tag":24,"props":412,"children":413},{},[414],{"type":15,"value":415},"truly strong interaction",{"type":15,"value":417}," would keep the ligand bound ",{"type":9,"tag":24,"props":419,"children":420},{},[421],{"type":15,"value":422},"for much longer times",{"type":15,"value":44},{"type":9,"tag":46,"props":425,"children":426},{},[],{"type":9,"tag":10,"props":428,"children":430},{"id":429},"_3-binding-energy-and-kd",[431],{"type":15,"value":432},"⚡ 3. Binding Energy and KD",{"type":9,"tag":18,"props":434,"children":435},{},[436,438,443],{"type":15,"value":437},"Binding strength can also be expressed as ",{"type":9,"tag":24,"props":439,"children":440},{},[441],{"type":15,"value":442},"binding free energy (ΔG)",{"type":15,"value":44},{"type":9,"tag":18,"props":445,"children":446},{},[447],{"type":15,"value":448},"Typical value discussed:",{"type":9,"tag":18,"props":450,"children":451},{},[452],{"type":9,"tag":102,"props":453,"children":454},{},[455],{"type":15,"value":456},"\nDelta G approx -35 ; kJ/mol\n",{"type":9,"tag":18,"props":458,"children":459},{},[460,462,467],{"type":15,"value":461},"This corresponds roughly to ",{"type":9,"tag":24,"props":463,"children":464},{},[465],{"type":15,"value":466},"micromolar binding affinity",{"type":15,"value":44},{"type":9,"tag":81,"props":469,"children":471},{"id":470},"important-insight",[472],{"type":15,"value":473},"Important insight",{"type":9,"tag":18,"props":475,"children":476},{},[477,479,484,486,491],{"type":15,"value":478},"Even though ",{"type":9,"tag":24,"props":480,"children":481},{},[482],{"type":15,"value":483},"−35 kJ/mol sounds like a lot",{"type":15,"value":485},", it still only stabilizes the interaction for ",{"type":9,"tag":24,"props":487,"children":488},{},[489],{"type":15,"value":490},"fractions of a second",{"type":15,"value":44},{"type":9,"tag":18,"props":493,"children":494},{},[495,497,502,504,509],{"type":15,"value":496},"To maintain ",{"type":9,"tag":24,"props":498,"children":499},{},[500],{"type":15,"value":501},"very stable complexes",{"type":15,"value":503},", the binding energy must be ",{"type":9,"tag":24,"props":505,"children":506},{},[507],{"type":15,"value":508},"much stronger",{"type":15,"value":44},{"type":9,"tag":46,"props":511,"children":512},{},[],{"type":9,"tag":10,"props":514,"children":516},{"id":515},"_4-why-ligands-dissociate-even-when-they-bind",[517],{"type":15,"value":518},"🔬 4. Why Ligands Dissociate (Even When They Bind)",{"type":9,"tag":18,"props":520,"children":521},{},[522],{"type":15,"value":523},"A key conceptual point in the lecture:",{"type":9,"tag":61,"props":525,"children":526},{},[527],{"type":9,"tag":18,"props":528,"children":529},{},[530,532,537],{"type":15,"value":531},"Binding interactions are ",{"type":9,"tag":24,"props":533,"children":534},{},[535],{"type":15,"value":536},"dynamic",{"type":15,"value":538},", not static.",{"type":9,"tag":18,"props":540,"children":541},{},[542,544,549],{"type":15,"value":543},"Proteins and ligands are constantly moving due to ",{"type":9,"tag":24,"props":545,"children":546},{},[547],{"type":15,"value":548},"thermal motion",{"type":15,"value":44},{"type":9,"tag":81,"props":551,"children":553},{"id":552},"molecular-motion-in-solution",[554],{"type":15,"value":555},"Molecular motion in solution",{"type":9,"tag":18,"props":557,"children":558},{},[559],{"type":15,"value":560},"In solution:",{"type":9,"tag":113,"props":562,"children":563},{},[564,574,584],{"type":9,"tag":117,"props":565,"children":566},{},[567,569],{"type":15,"value":568},"Molecules ",{"type":9,"tag":24,"props":570,"children":571},{},[572],{"type":15,"value":573},"vibrate",{"type":9,"tag":117,"props":575,"children":576},{},[577,579],{"type":15,"value":578},"They ",{"type":9,"tag":24,"props":580,"children":581},{},[582],{"type":15,"value":583},"rotate",{"type":9,"tag":117,"props":585,"children":586},{},[587,588],{"type":15,"value":578},{"type":9,"tag":24,"props":589,"children":590},{},[591],{"type":15,"value":592},"collide with solvent molecules",{"type":9,"tag":18,"props":594,"children":595},{},[596],{"type":15,"value":597},"Because of this motion:",{"type":9,"tag":113,"props":599,"children":600},{},[601,609,617],{"type":9,"tag":117,"props":602,"children":603},{},[604],{"type":9,"tag":24,"props":605,"children":606},{},[607],{"type":15,"value":608},"Hydrogen bonds break and reform",{"type":9,"tag":117,"props":610,"children":611},{},[612],{"type":9,"tag":24,"props":613,"children":614},{},[615],{"type":15,"value":616},"Electrostatic interactions fluctuate",{"type":9,"tag":117,"props":618,"children":619},{},[620],{"type":9,"tag":24,"props":621,"children":622},{},[623],{"type":15,"value":624},"Van der Waals contacts change",{"type":9,"tag":18,"props":626,"children":627},{},[628,630,635],{"type":15,"value":629},"Eventually, enough interactions break ",{"type":9,"tag":24,"props":631,"children":632},{},[633],{"type":15,"value":634},"simultaneously",{"type":15,"value":636},", allowing the ligand to escape.",{"type":9,"tag":18,"props":638,"children":639},{},[640,642,647],{"type":15,"value":641},"This is a ",{"type":9,"tag":24,"props":643,"children":644},{},[645],{"type":15,"value":646},"statistical process",{"type":15,"value":648}," driven by thermal energy.",{"type":9,"tag":46,"props":650,"children":651},{},[],{"type":9,"tag":10,"props":653,"children":655},{"id":654},"_5-types-of-interactions-holding-ligands-in-place",[656],{"type":15,"value":657},"🔗 5. Types of Interactions Holding Ligands in Place",{"type":9,"tag":18,"props":659,"children":660},{},[661,663,668],{"type":15,"value":662},"Protein–ligand binding typically relies on ",{"type":9,"tag":24,"props":664,"children":665},{},[666],{"type":15,"value":667},"non-covalent interactions",{"type":15,"value":669},", including:",{"type":9,"tag":81,"props":671,"children":673},{"id":672},"electrostatic-interactions",[674],{"type":15,"value":675},"Electrostatic interactions ⚡",{"type":9,"tag":18,"props":677,"children":678},{},[679],{"type":15,"value":680},"Attraction between opposite charges.",{"type":9,"tag":18,"props":682,"children":683},{},[684],{"type":15,"value":685},"Example:",{"type":9,"tag":113,"props":687,"children":688},{},[689],{"type":9,"tag":117,"props":690,"children":691},{},[692],{"type":15,"value":693},"Lysine (+) interacting with a negatively charged ligand group.",{"type":9,"tag":81,"props":695,"children":697},{"id":696},"hydrogen-bonds",[698],{"type":15,"value":699},"Hydrogen bonds 🔗",{"type":9,"tag":18,"props":701,"children":702},{},[703],{"type":15,"value":704},"Directional interactions between:",{"type":9,"tag":113,"props":706,"children":707},{},[708,713],{"type":9,"tag":117,"props":709,"children":710},{},[711],{"type":15,"value":712},"donor (NH, OH)",{"type":9,"tag":117,"props":714,"children":715},{},[716],{"type":15,"value":717},"acceptor (O, N)",{"type":9,"tag":81,"props":719,"children":721},{"id":720},"van-der-waals-interactions",[722],{"type":15,"value":723},"Van der Waals interactions 🌌",{"type":9,"tag":18,"props":725,"children":726},{},[727,729,734],{"type":15,"value":728},"Weak contacts caused by ",{"type":9,"tag":24,"props":730,"children":731},{},[732],{"type":15,"value":733},"temporary dipoles between atoms",{"type":15,"value":44},{"type":9,"tag":46,"props":736,"children":737},{},[],{"type":9,"tag":81,"props":739,"children":741},{"id":740},"important-consequence",[742],{"type":15,"value":743},"Important consequence",{"type":9,"tag":18,"props":745,"children":746},{},[747,749,754],{"type":15,"value":748},"Because these interactions are ",{"type":9,"tag":24,"props":750,"children":751},{},[752],{"type":15,"value":753},"individually weak",{"type":15,"value":755},", the ligand can escape when:",{"type":9,"tag":113,"props":757,"children":758},{},[759],{"type":9,"tag":117,"props":760,"children":761},{},[762],{"type":15,"value":763},"several interactions break at the same time.",{"type":9,"tag":46,"props":765,"children":766},{},[],{"type":9,"tag":10,"props":768,"children":770},{"id":769},"️-6-molecular-dynamics-of-binding",[771],{"type":15,"value":772},"🎞️ 6. Molecular Dynamics of Binding",{"type":9,"tag":18,"props":774,"children":775},{},[776,778,783],{"type":15,"value":777},"The lecture showed a ",{"type":9,"tag":24,"props":779,"children":780},{},[781],{"type":15,"value":782},"simulation of an alginate trimer binding to a protein module",{"type":15,"value":44},{"type":9,"tag":18,"props":785,"children":786},{},[787],{"type":15,"value":788},"Key observations:",{"type":9,"tag":113,"props":790,"children":791},{},[792,803,814],{"type":9,"tag":117,"props":793,"children":794},{},[795,796,801],{"type":15,"value":352},{"type":9,"tag":24,"props":797,"children":798},{},[799],{"type":15,"value":800},"wiggles and vibrates",{"type":15,"value":802}," inside the binding pocket.",{"type":9,"tag":117,"props":804,"children":805},{},[806,808,813],{"type":15,"value":807},"Interactions ",{"type":9,"tag":24,"props":809,"children":810},{},[811],{"type":15,"value":812},"form and break continuously",{"type":15,"value":44},{"type":9,"tag":117,"props":815,"children":816},{},[817,819,824],{"type":15,"value":818},"Occasionally, the ligand gains enough energy to ",{"type":9,"tag":24,"props":820,"children":821},{},[822],{"type":15,"value":823},"leave the binding site",{"type":15,"value":44},{"type":9,"tag":18,"props":826,"children":827},{},[828],{"type":15,"value":829},"Timescale:",{"type":9,"tag":18,"props":831,"children":832},{},[833,835,840],{"type":15,"value":834},"⏱️ Dissociation events occur within ",{"type":9,"tag":24,"props":836,"children":837},{},[838],{"type":15,"value":839},"microseconds",{"type":15,"value":44},{"type":9,"tag":46,"props":842,"children":843},{},[],{"type":9,"tag":10,"props":845,"children":847},{"id":846},"_7-dissociation-frequency-example",[848],{"type":15,"value":849},"📊 7. Dissociation Frequency Example",{"type":9,"tag":18,"props":851,"children":852},{},[853,855,860],{"type":15,"value":854},"If the measured KD is ",{"type":9,"tag":24,"props":856,"children":857},{},[858],{"type":15,"value":859},"millimolar",{"type":15,"value":861},", dissociation can happen extremely frequently.",{"type":9,"tag":18,"props":863,"children":864},{},[865],{"type":15,"value":685},{"type":9,"tag":18,"props":867,"children":868},{},[869],{"type":9,"tag":102,"props":870,"children":871},{},[872],{"type":15,"value":873},"\n10^4 \text{ dissociation events per second}\n",{"type":9,"tag":18,"props":875,"children":876},{},[877],{"type":15,"value":344},{"type":9,"tag":113,"props":879,"children":880},{},[881],{"type":9,"tag":117,"props":882,"children":883},{},[884,886,891],{"type":15,"value":885},"The ligand can detach ",{"type":9,"tag":24,"props":887,"children":888},{},[889],{"type":15,"value":890},"10,000 times per second",{"type":15,"value":44},{"type":9,"tag":46,"props":893,"children":894},{},[],{"type":9,"tag":81,"props":896,"children":898},{"id":897},"important-concept",[899],{"type":15,"value":900},"Important concept",{"type":9,"tag":18,"props":902,"children":903},{},[904,906,911],{"type":15,"value":905},"Unlike association, ",{"type":9,"tag":24,"props":907,"children":908},{},[909],{"type":15,"value":910},"dissociation does NOT depend on concentration",{"type":15,"value":44},{"type":9,"tag":18,"props":913,"children":914},{},[915],{"type":15,"value":916},"Reason:",{"type":9,"tag":113,"props":918,"children":919},{},[920,931],{"type":9,"tag":117,"props":921,"children":922},{},[923,925,930],{"type":15,"value":924},"The ligand is ",{"type":9,"tag":24,"props":926,"children":927},{},[928],{"type":15,"value":929},"already bound",{"type":15,"value":44},{"type":9,"tag":117,"props":932,"children":933},{},[934],{"type":15,"value":935},"It does not need to find another molecule.",{"type":9,"tag":18,"props":937,"children":938},{},[939,941,946],{"type":15,"value":940},"Dissociation is governed purely by ",{"type":9,"tag":24,"props":942,"children":943},{},[944],{"type":15,"value":945},"internal molecular energy fluctuations",{"type":15,"value":44},{"type":9,"tag":46,"props":948,"children":949},{},[],{"type":9,"tag":10,"props":951,"children":953},{"id":952},"key-takeaways",[954],{"type":15,"value":955},"🧠 Key Takeaways",{"type":9,"tag":81,"props":957,"children":959},{"id":958},"_1️⃣-kd-measures-binding-affinity",[960],{"type":15,"value":961},"1️⃣ KD measures binding affinity",{"type":9,"tag":18,"props":963,"children":964},{},[965],{"type":15,"value":966},"Lower KD = stronger binding.",{"type":9,"tag":46,"props":968,"children":969},{},[],{"type":9,"tag":81,"props":971,"children":973},{"id":972},"_2️⃣-strong-binding-means-long-residence-time",[974],{"type":15,"value":975},"2️⃣ Strong binding means long residence time",{"type":9,"tag":18,"props":977,"children":978},{},[979],{"type":15,"value":980},"Weak binding leads to rapid dissociation.",{"type":9,"tag":46,"props":982,"children":983},{},[],{"type":9,"tag":81,"props":985,"children":987},{"id":986},"_3️⃣-proteinligand-complexes-are-dynamic",[988],{"type":15,"value":989},"3️⃣ Protein–ligand complexes are dynamic",{"type":9,"tag":18,"props":991,"children":992},{},[993],{"type":15,"value":994},"Interactions constantly break and reform.",{"type":9,"tag":46,"props":996,"children":997},{},[],{"type":9,"tag":81,"props":999,"children":1001},{"id":1000},"_4️⃣-dissociation-is-statistical",[1002],{"type":15,"value":1003},"4️⃣ Dissociation is statistical",{"type":9,"tag":18,"props":1005,"children":1006},{},[1007],{"type":15,"value":1008},"Thermal motion eventually breaks enough interactions for the ligand to escape.",{"type":9,"tag":46,"props":1010,"children":1011},{},[],{"type":9,"tag":81,"props":1013,"children":1015},{"id":1014},"_5️⃣-non-covalent-interactions-control-binding",[1016],{"type":15,"value":1017},"5️⃣ Non-covalent interactions control binding",{"type":9,"tag":18,"props":1019,"children":1020},{},[1021],{"type":15,"value":1022},"Examples include:",{"type":9,"tag":113,"props":1024,"children":1025},{},[1026,1031,1036],{"type":9,"tag":117,"props":1027,"children":1028},{},[1029],{"type":15,"value":1030},"hydrogen bonds",{"type":9,"tag":117,"props":1032,"children":1033},{},[1034],{"type":15,"value":1035},"electrostatics",{"type":9,"tag":117,"props":1037,"children":1038},{},[1039],{"type":15,"value":1040},"van der Waals forces",{"type":9,"tag":46,"props":1042,"children":1043},{},[],{"type":9,"tag":18,"props":1045,"children":1046},{},[1047,1049],{"type":15,"value":1048},"✅ ",{"type":9,"tag":24,"props":1050,"children":1051},{},[1052],{"type":15,"value":1053},"Core idea of the lecture:",{"type":9,"tag":61,"props":1055,"children":1056},{},[1057],{"type":9,"tag":18,"props":1058,"children":1059},{},[1060,1062],{"type":15,"value":1061},"Protein–ligand binding is not a rigid lock-and-key system.\nIt is a ",{"type":9,"tag":24,"props":1063,"children":1064},{},[1065],{"type":15,"value":1066},"dynamic equilibrium where molecules constantly bind and unbind due to thermal motion.",1775084284353]