Chem 27S - Biophysical Chemistry

Exam — Computer simulations of biological membranes and membrane proteins

/tnswer the questions below in a succinct and incisive manner.

1. Any ttttem, before underg0ih§ MD timuIation, need t0 be initialized. (11 points total)
a.What information or data about the timulatI0n fyttem need t0 be initialized? H0w are tLete
data initialized/(6 pointt)
b.In the ttudy on LydropLobic mitmatcL, LOW d0 y0u think the coordinatet 0ftLe WALP and WALP-
like peptidet were initialized/ What characterittict related t0tLe tecondary ttructure of tLete
peptidet could p0ffibly have been empl0ted t0 C0nttruct tLem/('i pointt)

2. F0rce fieIdt (12 points total)

a.What it a f0rce field in the context of MD timulatI0nf! (J §0Intt)
b.What are the comp0nentt 0ftLe CHARMM f0rcefield? (4 pointt)
c. In calculating the p0tential energiet between the particIet ofa timulatl0h fyttem, which force
field comp0nentt are the m0tt computationally expentive/ What common techniquet are
uted t0 addrett tLif C0ft! (J pointt)

1. TW0 water moIecuIet were initialized with the foII0WIng coordinatet (15 points total):

X
Water 1 01 0.J7870 -J.87939 -8.08769
H1a 0.12518 -S.88023 48488
HU 0.J2191 -8.7S08S -8.38907
Water 2 02 -1.4J62J -0.81820 7.82921
H2a -1.7J217 -0.98J90 6.7J412
H2b -0.7047J -1.5J817 7.d1860

and parametert

0-H bond
Equilibrium bond length (#0) in A 0.9'i72
Bond f0rce conttant(K›) in kcal/mol/A 4'i0.0

fl-0-fl angle
Equilibrium angle (𝜃) in radiant 1.824
 Angle f0rce c0nftant (𝐾𝜃) in
SS.0
l‹caI/m0Ie/rad l

Partial charget
0 -0.8J4
0.417

tennardUoneiparameten 𝜀 𝑟𝑚𝑖𝑛 𝜎𝑂−𝐻

0 -0.1521 1.7d82 0.08J0
-0.040 0.224'i

Using the f0II0Wif1g f0rce field functl0f1

U R) —— K/,(b — b0) 2

a) Whdt it the p0tential energy ariting from the b0nded termt/ PIeate tLow the math. (/
pointt)
L) In calculating the non-bonded interacti0n energiet, a cut-0ff radiut 0f10 AWdt iMp0ted to
Ietten the computational expente. Thdt it, bet0nd a distance of 16 A, the interaction between
tw0 at0Mf it neglected. With thit cut-0ffradiut, tet up the equation that will let y0u determine
the p0tential energy ariting from the non-L0nd interactiont. (both: The tubtcriptt i,j refer to the
tw0 at0Mt f0r which the non-bond interaction it being calculated. r/; refer t0 the distance
between at0mt iand t and g it the charge ofat0m i). (8 §0Ihtt)

4. In moving the particIet a ording t0 CIatticaI mecLanict, h0t 0nIy the f0rcet actihg 0n a particle
need t0 Le known but the duration with which thete forcet will be applied aIt0 need to Le
tpecified. (7 points total)
a. What ittuet need to Le balanced in deciding the length of the timulatl0n time ttep/ (J §0Intf)
b.What typically determinet the tL0rtett time ttep that can Le empl0ted in MD timulationt/ Are
there any techniquet c0MM0nly employed to Ietten the computational C0ft attociated with
very tmaII time ttept/ ('i pointt)

s. The c0ncept 0f an entemble of ttatet it central to Low ttatitticaI mecLanict it able to relate macr0scopic
0btervati0nf t0tLe microtc0§IC C0hfiguration ofa tyttem. (7 points total)
a. Whdt is a micr0canonical entemble and LOW It it different f[0M d canonical entemble/ (J pointt)
b.What entemble wat generated in the MitmatcL papers What variabIet were kept c0hftant! (4
points)

6. b/d[0§L0bic mitmatch (8 points total)

 a. What If b\b[0§b0bIC MitmdtcL? What are the ttpet of hyd[0§L0bic mitmatcLet/ (J
pointt)
b. What are the typical retpontet that can Le Observed for the different typet of hydropL0Lic
mitmatcLet/ (J §0Intt)

7. In the MitmatcL paper, PMFt f0rtLe different mitmatch retp0ntet were conttructed. (10 points)
a. Detcribe briefly h0w the PMF f0r Felix tilting w0uld have been conttructed. ('i pointt)
b. In the PMF f0r Felix tilting (Fig. la of the MitmatcL paper), Whdt d0tLe minima of the different
PMF curvet tignify/ What informatI0n Can Le deduced fr0m the broadnett 0ftLe PMF curvet/ ('i
pointt)

8. M0deling the platma membrane. (14 points total)

a. In termt of ttructural retolution 0ftLe timulation ttttem, what it the main difference between
the timulatl0n detailf 0ftLe MitmatcL add Ih§0Iftf0n ttudy/ (J pointt)
b. What were the force fieldt uted in the MitmatcL and IngoIftf0n papert/ (4 pointt)
c. Detcribe Low the computatI0naI cott-reducti0n technique employed in the Ingolftf0n ttudy it
implemented. (/ §0Ihtt)

9. Lipidt (11 points)

a.Under what conditiont would lipid m0leculet likely form lipid bilatert/ Micellet/ (4 §0Ihtf)
b. In general, what it the effect of cL0letterol 0n the Ordering 0f lipid bilayert/ Why/ (3
§0Intt)
c.Bated 0n Fig. 1c of the IngoIftf0n paper, what C0ncluti0f1 Can Le made regarding the
dittributi0f10f CLOIetterOI in the tw0 bilater leaflett/ (4 pointt)

10.Explain in Iayman’t termt what the g0al it 0f umbrella tampling. (S points)