موضوعات سمينار : Side chain dihedral roramer libraries Polarizable force fields Plop...

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موضوعات سمينار : Side chain dihedral roramer libraries Polarizable force fields Plop software Loop prediction Pk a prediction by simulation SMD simulation REMD simulation Δ G binding prediction by simulation Salvation model in simulation Inverse-docking - PowerPoint PPT Presentation

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:Side chain dihedral roramer librariesPolarizable force fieldsPlop softwareLoop prediction Pka prediction by simulationSMD simulation REMD simulation G binding prediction by simulation Salvation model in simulation Inverse-docking Replica exchange simulationQuantum molecular dynamics simulation Quantum Monte Carlo Biodetergent simulationSimulation in nano tecnonogy Nanobuiorobate simulationDNA computing Analysis with molecular dynamics simulation Normal Mode .... 2

(MM) (MD) (MC) (Docking)3MedicinalChemistryProteins fromNatural OrganismsLigands from Natural Sources or SynthesisPreparative BiochemistryAssay, CharacterizationCrystallizationX-RaySequence Database3D StructureGeneCloningGene synthesisSite-DirectedMutagenesisExpressionComputer GraphicsKnowledge BasedModelling and DesignCD, NMRSimulation byEM, MD, ...Molecular BiologyBiophysics BiocomputingOrganic chemistryProtein-LigandComplex 45 : . :

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Structural biologyComputational chemistryMedicinalchemistry Biochemistry - .... -

7 :- . !- .CompanyProjectAir LiquideDesign zeolites for O2/N2 separationAir Prod & ChemAdhesives, adsorptionAlbemarleFlame retardancyAmocoCatalysis-homo/heterogeneous, thermochemistryDuPontThermo, kinetics, catalysisExxon R&ENOx kinetics, elementary and networked reactions, safetyProcter & GambleDesigned detergent enzymeHerculesPolysaccharide rheology 8 0000,10010019500000,10010019601000,000,2000,1529819702000,300000,2049619804000,100000,3089219908000,50000,401288199515000,20000,502080200025000,10000,703070200530000,5000,1004050201040000,2000,1405050201560000,1802020209Drug design for Diabetes Type IIWilliam Lipscombfalcipain inhibitors Ring et al. Proc. Natl. Acad. Sci. USA, 90, 3583-3587 (1993)FluA HA fusion inhibitors Bodian et al., Biochemistry, 32, 2967-3978 (1993)HIV Tat-TAR interaction inhibitors Filikov et al. J. Comput-Aided Mol. Des. 12, 229-240 (1998)CD4-MHC II inhibitors Gao et al. Proc. Natl. Acad. Sci. USA., 94, 73-78 (1997) HIV gp41 inhibitors Debnath et al.; J. Med. Chem, 42, 3203-3209 (1999)aquaporin-1 mechanismB. de Groot & H. Grubmller,Science 294: 2353-2357 (2001)photo-isomerizationG. Groenhof et al.,J. Am. Chem. Soc. 126:4228-4233 ,(2004)reaction pathwaysDiels-Alder cyclo-addition mechanismExamples and Success Stories

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11computer-aided design and draftingBiocomputing:

Intersection of Biology and Computation

Bioinformatics : This includes management of biological databases, data mining and data modeling, as well as IT-tools for data visualization

Computational Biology : This includes efforts to solve biological problems with computational tools (such as modeling, algorithms, heuristics)

DNA computing and nano-engineering : This includes models and experiments to use DNA (and other) molecules to perform computations

Computations in living organisms : this is concerned with constructing computational components in living cells, as well as with studying computational processes taking place daily in living organisms.

Computational chemistry:

13 : : 1- (MM) : Hyperchem

2- (MC):

3- (MD): . 4- : : (ab inititio) ((Semiemperical Density function theory)) Games Orca ...

5- - (Molecular Mechanic- Quntum Mechanic ) : ( ) ( ) ( ZPE= )- .

PES (Force field): ..

:

: -

- :

r0

16

:

17

B-C A-B-C-D n=3 ethanen=2 ethylenen=1 butane

: ABC BCD BC ( )18HHHHHHNewmanprojection0= 60=

n (multiplicity) Improper torsions and out of plane bending motions

19 - - ..

: : : : : 1 : :

: : ( (dispersion))20

: - 5 - 2 . req0N3.50.16C3.40.12 :

rm - 21 2r0

0 Pka : pH

HA H+ + A- pH = pKa : [A-] = [HA]

pH > pKa : [A-] > [HA]

pH < pKa : [A-] < [HA]

pKa : pka . : Pka . pka propka , H++pKa : 4pKa : 11 Pka : 6.5 : pKa= -log Ka ka = [H+] [A-][HA]

Pka : 22 (q) = pH (PI) : pH pH = pH

= Pka-pH pH =

PI-pH = : : pH : : 23

( )( )

:

:

( ) : ( ) : -

1 I

24 : :F=q1q2/r2 ( ) : q1 . : E=F/q2 =q1/r2

() : q r : =q/r

()

U: q1 q2 : U=w= Fr=q1q2/r2 r=q1q2/rV : U=q2=q1q2/r

25 : : :

The electrostatics scheme colors each vertex on the surface according to the electrostatic potential at that vertex using a red-to-blue gradient from -7.0 to +10.0

= 78 80 = 3 = 1

: : : 26 = 80 1.5 = 3 40 : : pH

140 27

- AcceptorD-H :A- Donor O, NO, N, F : 3.1 2.7 - : 5 :A-CD-H