{[ promptMessage ]}

Bookmark it

{[ promptMessage ]}

Chem167_L12_May14

whereasre likely to be less usefulpositions tfhey

Info icon This preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: search t o t he docking o molecules b simbased gridenergetically favorablefpositions forythese smaller fragments h as been to calculate, ~ e n t l y ulated annealing a re simpler described r esuch po- . ~ Whereasre likely to be less usefulpositions tfhey hese sitions a energetically favorable because or t may smaller fragments a re simpleratoarger ligand. Morebe sterically unattainable for l calculate, such positionsn t he ikely toofe igands i t is because they have over, i a re l design b l less useful important t o may orientational, a s well a f p a larger information be sterically unattainable s or ositional,ligand. More- Computa9onal solvent mapping Computa9onal solvent mapping •  14 organic probes to flood receptor surface •  Probes clustered and ranked by interac/on energy with surface •  Hot spots indicate areas of high func/onal group affinity Brenke R, Kozakov D, Chuang G- Y, Beglov D, MaYos C, and Vajda S, Bioinforma/cs. hYp://]map.bu.edu/ De novo approaches (LUDI) Predic9ng PK proper9es QikProp (Schrodinger): -   octanol/water par//on coefficient and water/gas logP’s -   Overall CNS ac/vity (BBB permeability) -   Caco- 2 and MDCK cell permeabili/es -   Assessments of serum albumin binding -   Predic/on of metabolites -   Assessment of “drug- likeness”, Lipinski’s “rule- of- five” ~40% of drug candidates fail in clinical trials because of poor ADME proper:es Grand challenge areas Protein folding & Protein- protein docking D. Baker Lab, U Washington Combinatorial Chemistry Chapter 16 May 13, 2013 What are some different ways to generate lead compounds? Lead genera/on Disadvantages of tradi9onal med chem? Complex and /me consuming Insufficient diversity for new lead discovery Synthe/c output too small Slow development of SAR profiles within a class of compounds •  Slow op/miza/on in evolu/onary cycles •  Insufficient patent coverage •  High costs •  •  •  •  Combinatorial chem •  Uses molecular scaffolds to construct libraries of similar compounds •  Allows high throughput screening (HTS) to search through many similar lead compounds •  Exploits instrumenta/on & robo/cs + computers to efficiently control rxn processes and analyze resul/ng data •  Success tends to depend on the complexity of the...
View Full Document

{[ snackBarMessage ]}

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern