Vicky ChoiDepartment of Computer Science Duke University

Outline

Local Improvement Basic Idea Details of Each Step Current Results Work in Progress

Protein Docking Problem (bound case)

.5))(,(&maximized))(,(

s.t.motionrigidafind

},1:),{(},1:),{( Given

BABumpisBAScore

misbBnjraA iijj

““local”

local”

(a,r) (b,s)

5.1Score:

(a,r) (b,s)

Bump:

Local Improvement

A

B

Basic Idea

:

Goal Tentative 1.Compute

)},s{(b B)} ,s{(cC iiii

minimized is )(

:),,(tchingWeightedMa .22

iiii cbw

CBw

.5))(',Bump(

s.t. ' :n ResolutioCollision.3

BA

?),())(',( Does BAScoreBAScore

A BA C B

1.Compute Tentative Goal

}:),{(

,),(eachFor

DsbaAraA

Bsb

iiai

ii

0),(

]1,0[ ))(,(),(:)( 0

ii

iiiiii

cABump

ttbAScorecAScoretbc

[0,1] t)()( iiii bAtbtb

) if0(0

}{min),(

iii

iaiArai

Aww

srcawia

2. Weighted Matching

minimized is )(

:),,(tchingWeightedMa 2

i

iii cbw

CBw

)()()( wwBBCBRB

w

3. Collision Resolution

521

0

10

,,,

0.) )()(,(

then,minLet

bump.ut witho

anslationlargest tr thebelet

),(),( eachfor

0),()(consider

,0))(,( If

:0))(,( Suppose

TTT

BCTBRABump

tT

t

BRsb

tBCtBR

BRABump

BABump

B

imi

i

Bii

B

B

3. Collision Resolution (Cont.)

40 ,4

),(: R

: vary and uFix

axis rotation thealong directedr unit vectoa is

rotation, theof magnitude theis where),(:

:0))(,( If

kku

u

uR

BRABump

kkk

B

Example 1: 1BRS (patches)

Native Input Correspondence Rotation Rotation + Translation Collision Resolution[304, 2] [26, 0] [466, 0] [44, 0] [342, 35] [122, 5]

RMSD=3.29 RMSD=1.83

[44, 0] [491, 0] [25, 0] [319, 10] [248, 5]RMSD=3.21 RMSD=0.69

[Score, Bump]

Example 2: 1BRSNative Input Correspondence Rotation Rotation + Translation Collision Resolution[309, 2] [10, 0] [313, 0] [22, 1] [171, 17] [29, 3]

RMSD=5.10 [17, 0] [151, 15] [35, 3][17, 0] [356, 0] [19, 0] [184, 25] [63, 5]

RMSD=5.01 RMSD=4.27

Example 3: 1BRS (non-docking site)Input Correspondence Rotation Rotation + Translation Collision Resolution

[13, 0] [226, 0] [5, 0] [193, 64] [23, 4]

[5, 0] [272, 0] [1, 0] [230, 71] [64, 5]

Example 4: 1CHONative Input Correspondence Rotation Rotation + Translation Collision Resolution[254, 1] [13, 0] [390, 0] [25, 1] [191, 20] [122, 5]

RMSD=4.44 [14,0] (1) [97, 3] [21, 0](t=0.214)[17, 0] [432, 0] [67, 4] [342, 38] [78,4]RMSD=3.21 [17, 0] (0) [117, 2] [231, 5]

RMSD=1.58

Work in Progress

A. varying neighborhood distance “D”;B. choosing the weights;C. trying jittering motions: C1. alternating between rotation and translation in pieces; C2. using a damping factor and iterating;D. adding hydrogens into the models.

Protein Docking Group @Duke

Pankaj K. AgarwalSergei BespamiatnykhVicky ChoiHerbert EdelsbrunnerAbhijit GuriaJohannes RudolphYusu Wang

VMD – Visual Molecular Dynamics: http://www.ks.uiuc.edu/Research/vmd