BCH 622 lecture notes Motions
(20160211: mod from 258 20100915 incl “Theme 4: Motions” & ED, alts, etc.)
Motions
• Assignment: WrkSht-motions.doc,
for Branden and Tooze kinemage c6FldFlx-KiNG.kin
• Assignment: Wrksht-Hemoglobin-Questions.pdf
for Hemoglobin allostery mechanism kinemage: HbAllo-KiNGques.kin
• Also:Look at B&T kins: c6, c8, c15 for features noted below…
• Also: Explore backrub motions and admire progression of tRNAs across the Ribosome
Handout pages attached: motions [p.11—15 + extra color plate]
NMR & x-ray : movements vs. multiple conformations vs errors or lack of information
but NMR sometimes directly measures motion: line width, ring flips
[p.11] time scales (nmr can now do faster)
fluctuations vs transitions
folding & allostery iin 2nd half of semester
[p.12] individual residues; xray low B vs multiple conformations vs disappear
nmr : ring flips; NH exchange
[p.13] loop motions – Staph. nuclease; protease sensitivity, ends not seen
HEW lysozyme: calc. vs. B’s (vs evolution)
TIM : order-disorder; entropy  specific but not too tight
(get some with any induced fit)
[p.14] domains (very common for catalysis or binding)
hexoKinase : specificity; exclude water; line up site
hinge motion : approx. rigid, but some bending
Graphics: ( B&T unmodified kinemages also on main website under Kinemages/Kins List)
(c15 k2)
a
(c8 k4)
(c6 k7) [p.14]
(c6 k8)
(c6 k9)
(c6 k5)
(c6 k6)
IgG flex
allostery : Trp repressor with Trp, DNA : 3 state
hexoK hinge
more unusual & dramatic: CDK2/cyclin
calmodulin
Gro EL/ES v1, slice; negative cooperativity
EL subunit : bow
Davis_Backrub_kinSup-mod.kin smooth backrub with two-state alternate conformations.
(in class show 1n9b ile 47 alts in electron density as a MolProbity run: e.g. dognpony160212.)
Ecoli70S_ratchet_demo.9.kin ratchet motion of 50S and 30S parts of the ribosome as tRNAs move
from Psite to Esite…
Electron Density, Alternate Conformations, and
Motions
• Mobile atoms can disappear:
Electron density smears out or fades,
high B-factors
• Fluctuations around one conformation vs
transitions between conformations.
Alternate conformations clear at high resolution
Different conformations seen between different chains or structures
• Scale: small local changes;
loop motion; domain motion;
allostery; molecular machines
• Simulations of motion
e.g., pathway: O2 into hemoglobin
transitions (better than "morphing")
• Experimental:
H exchange
NMR: degree of mobility; time scale (may disappear)
Crystal structures: see endpoints, but no time scale
• Equilibrium structure vs change vs ensemble